Using MTAG to enhance the GWAS ability #213
Comments
|
Hello Tian,
I'm a bit confused by your question. Are you worried that the very
significant results for rep_1 is spurious? If you post your log file, it
will help me understand what is going on better.
Best,
Patrick
…On Mon, May 20, 2024 at 4:06 AM real ***@***.***> wrote:
Hello,
I used MTAG to enhance the GWAS ability. I have phenotypic data of three
environments of plant hegiht which has low repeatability. We call the
rep_1,rep_2,rep_3. The GWAS signials were under 1e-5, but the MTAG signials
for rep_1 was under 1e-100, rep_2 and rep_3 were under 1e-5 that same as
the GWAS results. My question are 1) Is MATG suitable for improving the
detection ability of duplicate data？If so, Is rep_1 an abnormal result and
how to handle it？
Thank you very much!
Tian
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Hello Patrick
Thanks for your reply. Yes, I think the results for rep_1 is spurious. The Manhattan plots for GWAS and MATG as well as the log file were attatched.
Thank you very much!
Best,
Tian
At 2024-05-21 02:41:50, "paturley" ***@***.***> wrote:
Hello Tian,
I'm a bit confused by your question. Are you worried that the very
significant results for rep_1 is spurious? If you post your log file, it
will help me understand what is going on better.
Best,
Patrick
On Mon, May 20, 2024 at 4:06 AM real ***@***.***> wrote:
Hello,
I used MTAG to enhance the GWAS ability. I have phenotypic data of three
environments of plant hegiht which has low repeatability. We call the
rep_1,rep_2,rep_3. The GWAS signials were under 1e-5, but the MTAG signials
for rep_1 was under 1e-100, rep_2 and rep_3 were under 1e-5 that same as
the GWAS results. My question are 1) Is MATG suitable for improving the
detection ability of duplicate data？If so, Is rep_1 an abnormal result and
how to handle it？
Thank you very much!
Tian
—
Reply to this email directly, view it on GitHub
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2024/05/14/03:05:46 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
<>
<> MTAG: Multi-trait Analysis of GWAS
<> Version: 1.0.8
<> (C) 2017 Omeed Maghzian, Raymond Walters, and Patrick Turley
<> Harvard University Department of Economics / Broad Institute of MIT and Harvard
<> GNU General Public License v3
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
<> Note: It is recommended to run your own QC on the input before using this program.
<> Software-related correspondence: ***@***.***
<> All other correspondence: ***@***.***
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
Calling ./mtag.py \
--force \
--stream-stdout \
--ld-ref-panel /data/ttian/08-GWAS_1223/01_Emmax_1223/5M_Q_K/LDscores/ \
--sumstats phen_20_PG_tbn.txt.m.ps,phen_21_PG_tbn.txt.m.ps,phen_22_PG_tbn.txt.m.ps \
--out PG/phen_PG_tbn
#phen_20_PG_tbn(rep_1),phen_21_PG_tbn(rep_2),phen_22_PG_tbn(rep_3)
2024/05/14/03:05:46 PM Beginning MTAG analysis...
2024/05/14/03:05:46 PM MTAG will use the Z column for analyses.
2024/05/14/03:05:55 PM Read in Trait 1 summary statistics (5593073 SNPs) from phen_20_PG_tbn.txt.m.ps ...
2024/05/14/03:05:55 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:05:55 PM Munging Trait 1 <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
2024/05/14/03:05:55 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:05:55 PM Interpreting column names as follows:
2024/05/14/03:05:55 PM snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
2024/05/14/03:05:55 PM Reading sumstats from provided DataFrame into memory 10000000 SNPs at a time.
2024/05/14/03:06:04 PM Read 5593073 SNPs from --sumstats file.
Removed 0 SNPs with missing values.
Removed 0 SNPs with INFO <= None.
Removed 0 SNPs with MAF <= 0.01.
Removed 0 SNPs with SE <0 or NaN values.
Removed 0 SNPs with out-of-bounds p-values.
Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs were not dropped.
5099629 SNPs remain.
2024/05/14/03:06:08 PM Removed 0 SNPs with duplicated rs numbers (5099629 SNPs remain).
2024/05/14/03:06:09 PM Removed 0 SNPs with N < 815.333333333 (5099629 SNPs remain).
2024/05/14/03:06:22 PM Median value of SIGNED_SUMSTAT was 0.000275905, which seems sensible.
2024/05/14/03:06:22 PM Dropping snps with null values
2024/05/14/03:06:22 PM
Metadata:
2024/05/14/03:06:23 PM Mean chi^2 = 0.941
2024/05/14/03:06:23 PM WARNING: mean chi^2 may be too small.
2024/05/14/03:06:23 PM Lambda GC = 0.912
2024/05/14/03:06:23 PM Max chi^2 = 30.569
2024/05/14/03:06:23 PM 1 Genome-wide significant SNPs (some may have been removed by filtering).
2024/05/14/03:06:23 PM
Conversion finished at Tue May 14 15:06:23 2024
2024/05/14/03:06:23 PM Total time elapsed: 28.06s
2024/05/14/03:06:33 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:33 PM Munging of Trait 1 complete. SNPs remaining: 5099629
2024/05/14/03:06:33 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:33 PM Warning: The mean chi2 statistic of trait 1 is less 1.02 - MTAG estimates may be unstable.
2024/05/14/03:06:51 PM Read in Trait 2 summary statistics (5593073 SNPs) from phen_21_PG_tbn.txt.m.ps ...
2024/05/14/03:06:51 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:51 PM Munging Trait 2 <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
2024/05/14/03:06:51 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:51 PM Interpreting column names as follows:
2024/05/14/03:06:51 PM snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
2024/05/14/03:06:51 PM Reading sumstats from provided DataFrame into memory 10000000 SNPs at a time.
2024/05/14/03:07:00 PM Read 5593073 SNPs from --sumstats file.
Removed 0 SNPs with missing values.
Removed 0 SNPs with INFO <= None.
Removed 0 SNPs with MAF <= 0.01.
Removed 0 SNPs with SE <0 or NaN values.
Removed 0 SNPs with out-of-bounds p-values.
Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs were not dropped.
5099629 SNPs remain.
2024/05/14/03:07:03 PM Removed 0 SNPs with duplicated rs numbers (5099629 SNPs remain).
2024/05/14/03:07:04 PM Removed 0 SNPs with N < 815.333333333 (5099629 SNPs remain).
2024/05/14/03:07:18 PM Median value of SIGNED_SUMSTAT was 0.0122005, which seems sensible.
2024/05/14/03:07:18 PM Dropping snps with null values
2024/05/14/03:07:18 PM
Metadata:
2024/05/14/03:07:19 PM Mean chi^2 = 0.933
2024/05/14/03:07:19 PM WARNING: mean chi^2 may be too small.
2024/05/14/03:07:19 PM Lambda GC = 0.91
2024/05/14/03:07:19 PM Max chi^2 = 25.301
2024/05/14/03:07:19 PM 0 Genome-wide significant SNPs (some may have been removed by filtering).
2024/05/14/03:07:19 PM
Conversion finished at Tue May 14 15:07:19 2024
2024/05/14/03:07:19 PM Total time elapsed: 28.61s
2024/05/14/03:07:28 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:28 PM Munging of Trait 2 complete. SNPs remaining: 5099629
2024/05/14/03:07:28 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:28 PM Warning: The mean chi2 statistic of trait 2 is less 1.02 - MTAG estimates may be unstable.
2024/05/14/03:07:47 PM Read in Trait 3 summary statistics (5593073 SNPs) from phen_22_PG_tbn.txt.m.ps ...
2024/05/14/03:07:47 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:47 PM Munging Trait 3 <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
2024/05/14/03:07:47 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:47 PM Interpreting column names as follows:
2024/05/14/03:07:47 PM snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
2024/05/14/03:07:47 PM Reading sumstats from provided DataFrame into memory 10000000 SNPs at a time.
2024/05/14/03:07:58 PM Read 5593073 SNPs from --sumstats file.
Removed 0 SNPs with missing values.
Removed 0 SNPs with INFO <= None.
Removed 0 SNPs with MAF <= 0.01.
Removed 0 SNPs with SE <0 or NaN values.
Removed 0 SNPs with out-of-bounds p-values.
Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs were not dropped.
5099629 SNPs remain.
2024/05/14/03:08:02 PM Removed 0 SNPs with duplicated rs numbers (5099629 SNPs remain).
2024/05/14/03:08:03 PM Removed 0 SNPs with N < 815.333333333 (5099629 SNPs remain).
2024/05/14/03:08:16 PM Median value of SIGNED_SUMSTAT was 0.00952361, which seems sensible.
2024/05/14/03:08:17 PM Dropping snps with null values
2024/05/14/03:08:17 PM
Metadata:
2024/05/14/03:08:18 PM Mean chi^2 = 0.951
2024/05/14/03:08:18 PM WARNING: mean chi^2 may be too small.
2024/05/14/03:08:18 PM Lambda GC = 0.934
2024/05/14/03:08:18 PM Max chi^2 = 31.856
2024/05/14/03:08:18 PM 3 Genome-wide significant SNPs (some may have been removed by filtering).
2024/05/14/03:08:18 PM
Conversion finished at Tue May 14 15:08:18 2024
2024/05/14/03:08:18 PM Total time elapsed: 31.07s
2024/05/14/03:08:29 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:08:29 PM Munging of Trait 3 complete. SNPs remaining: 5099629
2024/05/14/03:08:29 PM <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:08:30 PM Warning: The mean chi2 statistic of trait 3 is less 1.02 - MTAG estimates may be unstable.
2024/05/14/03:08:46 PM Dropped 737230 SNPs due to strand ambiguity, 4362399 SNPs remain in intersection after merging trait1
2024/05/14/03:09:03 PM Dropped 0 SNPs due to strand ambiguity, 4362399 SNPs remain in intersection after merging trait2
2024/05/14/03:09:22 PM Dropped 0 SNPs due to strand ambiguity, 4362399 SNPs remain in intersection after merging trait3
2024/05/14/03:09:22 PM ... Merge of GWAS summary statistics complete. Number of SNPs: 4362399
2024/05/14/03:09:38 PM Using 4362399 SNPs to estimate Omega (0 SNPs excluded due to strand ambiguity)
2024/05/14/03:09:38 PM Estimating sigma..
2024/05/14/03:14:29 PM Checking for positive definiteness ..
2024/05/14/03:14:29 PM Sigma hat:
[[1.165 0.97 0.88 ]
[0.97 1.177 0.914]
[0.88 0.914 1.131]]
2024/05/14/03:14:29 PM Mean chi^2 of SNPs used to estimate Omega is low for some SNPsMTAG may not perform well in this situation.
2024/05/14/03:14:30 PM Beginning estimation of Omega ...
2024/05/14/03:14:30 PM Using GMM estimator of Omega ..
2024/05/14/03:14:31 PM Checking for positive definiteness ..
2024/05/14/03:14:31 PM matrix is not positive definite, performing adjustment..
2024/05/14/03:14:31 PM Warning: max number of iterations reached in adjustment procedure. Sigma matrix used is still non-positive-definite.
2024/05/14/03:14:31 PM Completed estimation of Omega ...
2024/05/14/03:14:31 PM Beginning MTAG calculations...
2024/05/14/03:15:19 PM ... Completed MTAG calculations.
2024/05/14/03:15:19 PM Writing Phenotype 1 to file ...
2024/05/14/03:15:58 PM Writing Phenotype 2 to file ...
2024/05/14/03:16:35 PM Writing Phenotype 3 to file ...
2024/05/14/03:17:15 PM
Summary of MTAG results:
------------------------
Trait # SNPs used N (max) N (mean) GWAS mean chi^2 MTAG mean chi^2 GWAS equiv. (max) N
1 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.807 18.926 -113599
2 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.792 1.771 -4537
3 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.841 1.444 -3409
Estimated Omega:
[[-1.839e-04 -6.803e-09 -5.303e-09]
[-6.803e-09 -2.001e-04 -5.786e-09]
[-5.303e-09 -5.786e-09 -1.472e-04]]
(Correlation):
[[nan nan nan]
[nan nan nan]
[nan nan nan]]
Estimated Sigma:
[[1.165 0.97 0.88 ]
[0.97 1.177 0.914]
[0.88 0.914 1.131]]
(Correlation):
[[1. 0.828 0.767]
[0.828 1. 0.792]
[0.767 0.792 1. ]]
MTAG weight factors: (average across SNPs)
[-0.014 -0.035 0.061]
2024/05/14/03:17:15 PM
2024/05/14/03:17:15 PM MTAG results saved to file.
2024/05/14/03:17:15 PM MTAG complete. Time elapsed: 11.0m:29.370085001s
|
|
Ah. So the problem is that your mean chi2 statistics are less than one, so
the implicit heritability is negative. I generally recommend that MTAG not
be used unless the mean chi2 is at least 1.1 for each trait. Better if it's
even higher than that. In your particular case, I think MTAG may not be the
right tool.
…On Mon, May 20, 2024 at 9:53 PM real ***@***.***> wrote:
Hello Patrick
Thanks for your reply. Yes, I think the results for rep_1 is spurious. The
Manhattan plots for GWAS and MATG as well as the log file were attatched.
Thank you very much!
Best,
Tian
At 2024-05-21 02:41:50, "paturley" ***@***.***> wrote:
Hello Tian,
I'm a bit confused by your question. Are you worried that the very
significant results for rep_1 is spurious? If you post your log file, it
will help me understand what is going on better.
Best,
Patrick
On Mon, May 20, 2024 at 4:06 AM real ***@***.***> wrote:
> Hello,
>
> I used MTAG to enhance the GWAS ability. I have phenotypic data of three
> environments of plant hegiht which has low repeatability. We call the
> rep_1,rep_2,rep_3. The GWAS signials were under 1e-5, but the MTAG
signials
> for rep_1 was under 1e-100, rep_2 and rep_3 were under 1e-5 that same as
> the GWAS results. My question are 1) Is MATG suitable for improving the
> detection ability of duplicate data？If so, Is rep_1 an abnormal result
and
> how to handle it？
>
> Thank you very much!
>
> Tian
>
> —
> Reply to this email directly, view it on GitHub
> <#213>, or unsubscribe
> <
https://github.com/notifications/unsubscribe-auth/AFBUB5LNIGHOATZ7YCQTGRLZDGVHZAVCNFSM6AAAAABH7H4OY2VHI2DSMVQWIX3LMV43ASLTON2WKOZSGMYDKMZYGM4DSMI
>
> .
> You are receiving this because you are subscribed to this thread.Message
> ID: ***@***.***>
>
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***@***.***>
2024/05/14/03:05:46 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
<>
<> MTAG: Multi-trait Analysis of GWAS
<> Version: 1.0.8
<> (C) 2017 Omeed Maghzian, Raymond Walters, and Patrick Turley
<> Harvard University Department of Economics / Broad Institute of MIT and
Harvard
<> GNU General Public License v3
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
<> Note: It is recommended to run your own QC on the input before using
this program.
<> Software-related correspondence: ***@***.***
<> All other correspondence: ***@***.***
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
Calling ./mtag.py \
--force \
--stream-stdout \
--ld-ref-panel /data/ttian/08-GWAS_1223/01_Emmax_1223/5M_Q_K/LDscores/ \
--sumstats phen_20_PG_tbn.txt.m.ps,phen_21_PG_tbn.txt.m.ps,
phen_22_PG_tbn.txt.m.ps \
--out PG/phen_PG_tbn
#phen_20_PG_tbn(rep_1),phen_21_PG_tbn(rep_2),phen_22_PG_tbn(rep_3)
2024/05/14/03:05:46 PM Beginning MTAG analysis...
2024/05/14/03:05:46 PM MTAG will use the Z column for analyses.
2024/05/14/03:05:55 PM Read in Trait 1 summary statistics (5593073 SNPs)
from phen_20_PG_tbn.txt.m.ps ...
2024/05/14/03:05:55 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:05:55 PM Munging Trait 1
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
2024/05/14/03:05:55 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:05:55 PM Interpreting column names as follows:
2024/05/14/03:05:55 PM snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
2024/05/14/03:05:55 PM Reading sumstats from provided DataFrame into
memory 10000000 SNPs at a time.
2024/05/14/03:06:04 PM Read 5593073 SNPs from --sumstats file.
Removed 0 SNPs with missing values.
Removed 0 SNPs with INFO <= None.
Removed 0 SNPs with MAF <= 0.01.
Removed 0 SNPs with SE <0 or NaN values.
Removed 0 SNPs with out-of-bounds p-values.
Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
were not dropped.
5099629 SNPs remain.
2024/05/14/03:06:08 PM Removed 0 SNPs with duplicated rs numbers (5099629
SNPs remain).
2024/05/14/03:06:09 PM Removed 0 SNPs with N < 815.333333333 (5099629 SNPs
remain).
2024/05/14/03:06:22 PM Median value of SIGNED_SUMSTAT was 0.000275905,
which seems sensible.
2024/05/14/03:06:22 PM Dropping snps with null values
2024/05/14/03:06:22 PM
Metadata:
2024/05/14/03:06:23 PM Mean chi^2 = 0.941
2024/05/14/03:06:23 PM WARNING: mean chi^2 may be too small.
2024/05/14/03:06:23 PM Lambda GC = 0.912
2024/05/14/03:06:23 PM Max chi^2 = 30.569
2024/05/14/03:06:23 PM 1 Genome-wide significant SNPs (some may have been
removed by filtering).
2024/05/14/03:06:23 PM
Conversion finished at Tue May 14 15:06:23 2024
2024/05/14/03:06:23 PM Total time elapsed: 28.06s
2024/05/14/03:06:33 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:33 PM Munging of Trait 1 complete. SNPs remaining: 5099629
2024/05/14/03:06:33 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:33 PM Warning: The mean chi2 statistic of trait 1 is less
1.02 - MTAG estimates may be unstable.
2024/05/14/03:06:51 PM Read in Trait 2 summary statistics (5593073 SNPs)
from phen_21_PG_tbn.txt.m.ps ...
2024/05/14/03:06:51 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:51 PM Munging Trait 2
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
2024/05/14/03:06:51 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:51 PM Interpreting column names as follows:
2024/05/14/03:06:51 PM snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
2024/05/14/03:06:51 PM Reading sumstats from provided DataFrame into
memory 10000000 SNPs at a time.
2024/05/14/03:07:00 PM Read 5593073 SNPs from --sumstats file.
Removed 0 SNPs with missing values.
Removed 0 SNPs with INFO <= None.
Removed 0 SNPs with MAF <= 0.01.
Removed 0 SNPs with SE <0 or NaN values.
Removed 0 SNPs with out-of-bounds p-values.
Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
were not dropped.
5099629 SNPs remain.
2024/05/14/03:07:03 PM Removed 0 SNPs with duplicated rs numbers (5099629
SNPs remain).
2024/05/14/03:07:04 PM Removed 0 SNPs with N < 815.333333333 (5099629 SNPs
remain).
2024/05/14/03:07:18 PM Median value of SIGNED_SUMSTAT was 0.0122005, which
seems sensible.
2024/05/14/03:07:18 PM Dropping snps with null values
2024/05/14/03:07:18 PM
Metadata:
2024/05/14/03:07:19 PM Mean chi^2 = 0.933
2024/05/14/03:07:19 PM WARNING: mean chi^2 may be too small.
2024/05/14/03:07:19 PM Lambda GC = 0.91
2024/05/14/03:07:19 PM Max chi^2 = 25.301
2024/05/14/03:07:19 PM 0 Genome-wide significant SNPs (some may have been
removed by filtering).
2024/05/14/03:07:19 PM
Conversion finished at Tue May 14 15:07:19 2024
2024/05/14/03:07:19 PM Total time elapsed: 28.61s
2024/05/14/03:07:28 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:28 PM Munging of Trait 2 complete. SNPs remaining: 5099629
2024/05/14/03:07:28 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:28 PM Warning: The mean chi2 statistic of trait 2 is less
1.02 - MTAG estimates may be unstable.
2024/05/14/03:07:47 PM Read in Trait 3 summary statistics (5593073 SNPs)
from phen_22_PG_tbn.txt.m.ps ...
2024/05/14/03:07:47 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:47 PM Munging Trait 3
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
2024/05/14/03:07:47 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:47 PM Interpreting column names as follows:
2024/05/14/03:07:47 PM snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
2024/05/14/03:07:47 PM Reading sumstats from provided DataFrame into
memory 10000000 SNPs at a time.
2024/05/14/03:07:58 PM Read 5593073 SNPs from --sumstats file.
Removed 0 SNPs with missing values.
Removed 0 SNPs with INFO <= None.
Removed 0 SNPs with MAF <= 0.01.
Removed 0 SNPs with SE <0 or NaN values.
Removed 0 SNPs with out-of-bounds p-values.
Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
were not dropped.
5099629 SNPs remain.
2024/05/14/03:08:02 PM Removed 0 SNPs with duplicated rs numbers (5099629
SNPs remain).
2024/05/14/03:08:03 PM Removed 0 SNPs with N < 815.333333333 (5099629 SNPs
remain).
2024/05/14/03:08:16 PM Median value of SIGNED_SUMSTAT was 0.00952361,
which seems sensible.
2024/05/14/03:08:17 PM Dropping snps with null values
2024/05/14/03:08:17 PM
Metadata:
2024/05/14/03:08:18 PM Mean chi^2 = 0.951
2024/05/14/03:08:18 PM WARNING: mean chi^2 may be too small.
2024/05/14/03:08:18 PM Lambda GC = 0.934
2024/05/14/03:08:18 PM Max chi^2 = 31.856
2024/05/14/03:08:18 PM 3 Genome-wide significant SNPs (some may have been
removed by filtering).
2024/05/14/03:08:18 PM
Conversion finished at Tue May 14 15:08:18 2024
2024/05/14/03:08:18 PM Total time elapsed: 31.07s
2024/05/14/03:08:29 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:08:29 PM Munging of Trait 3 complete. SNPs remaining: 5099629
2024/05/14/03:08:29 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:08:30 PM Warning: The mean chi2 statistic of trait 3 is less
1.02 - MTAG estimates may be unstable.
2024/05/14/03:08:46 PM Dropped 737230 SNPs due to strand ambiguity,
4362399 SNPs remain in intersection after merging trait1
2024/05/14/03:09:03 PM Dropped 0 SNPs due to strand ambiguity, 4362399
SNPs remain in intersection after merging trait2
2024/05/14/03:09:22 PM Dropped 0 SNPs due to strand ambiguity, 4362399
SNPs remain in intersection after merging trait3
2024/05/14/03:09:22 PM ... Merge of GWAS summary statistics complete.
Number of SNPs: 4362399
2024/05/14/03:09:38 PM Using 4362399 SNPs to estimate Omega (0 SNPs
excluded due to strand ambiguity)
2024/05/14/03:09:38 PM Estimating sigma..
2024/05/14/03:14:29 PM Checking for positive definiteness ..
2024/05/14/03:14:29 PM Sigma hat:
[[1.165 0.97 0.88 ]
[0.97 1.177 0.914]
[0.88 0.914 1.131]]
2024/05/14/03:14:29 PM Mean chi^2 of SNPs used to estimate Omega is low
for some SNPsMTAG may not perform well in this situation.
2024/05/14/03:14:30 PM Beginning estimation of Omega ...
2024/05/14/03:14:30 PM Using GMM estimator of Omega ..
2024/05/14/03:14:31 PM Checking for positive definiteness ..
2024/05/14/03:14:31 PM matrix is not positive definite, performing
adjustment..
2024/05/14/03:14:31 PM Warning: max number of iterations reached in
adjustment procedure. Sigma matrix used is still non-positive-definite.
2024/05/14/03:14:31 PM Completed estimation of Omega ...
2024/05/14/03:14:31 PM Beginning MTAG calculations...
2024/05/14/03:15:19 PM ... Completed MTAG calculations.
2024/05/14/03:15:19 PM Writing Phenotype 1 to file ...
2024/05/14/03:15:58 PM Writing Phenotype 2 to file ...
2024/05/14/03:16:35 PM Writing Phenotype 3 to file ...
2024/05/14/03:17:15 PM
Summary of MTAG results:
------------------------
Trait # SNPs used N (max) N (mean) GWAS mean chi^2 MTAG mean chi^2 GWAS
equiv. (max) N
1 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.807 18.926 -113599
2 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.792 1.771 -4537
3 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.841 1.444 -3409
Estimated Omega:
[[-1.839e-04 -6.803e-09 -5.303e-09]
[-6.803e-09 -2.001e-04 -5.786e-09]
[-5.303e-09 -5.786e-09 -1.472e-04]]
(Correlation):
[[nan nan nan]
[nan nan nan]
[nan nan nan]]
Estimated Sigma:
[[1.165 0.97 0.88 ]
[0.97 1.177 0.914]
[0.88 0.914 1.131]]
(Correlation):
[[1. 0.828 0.767]
[0.828 1. 0.792]
[0.767 0.792 1. ]]
MTAG weight factors: (average across SNPs)
[-0.014 -0.035 0.061]
2024/05/14/03:17:15 PM
2024/05/14/03:17:15 PM MTAG results saved to file.
2024/05/14/03:17:15 PM MTAG complete. Time elapsed: 11.0m:29.370085001s
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Hello Patrick
Thanks for your reply. I find that the mean chr^2 of my GWAS results for all the traits were less than 1. My phenotype data includes plant height, leaf angle and tassel branch numbers, etc which have higher broad sense heritability.Where could this be the problems?
Thank you and all the best,
Tian
At 2024-05-22 04:40:51, "paturley" ***@***.***> wrote:
Ah. So the problem is that your mean chi2 statistics are less than one, so
the implicit heritability is negative. I generally recommend that MTAG not
be used unless the mean chi2 is at least 1.1 for each trait. Better if it's
even higher than that. In your particular case, I think MTAG may not be the
right tool.
On Mon, May 20, 2024 at 9:53 PM real ***@***.***> wrote:
Hello Patrick
Thanks for your reply. Yes, I think the results for rep_1 is spurious. The
Manhattan plots for GWAS and MATG as well as the log file were attatched.
Thank you very much!
Best,
Tian
At 2024-05-21 02:41:50, "paturley" ***@***.***> wrote:
Hello Tian,
I'm a bit confused by your question. Are you worried that the very
significant results for rep_1 is spurious? If you post your log file, it
will help me understand what is going on better.
Best,
Patrick
On Mon, May 20, 2024 at 4:06 AM real ***@***.***> wrote:
> Hello,
>
> I used MTAG to enhance the GWAS ability. I have phenotypic data of three
> environments of plant hegiht which has low repeatability. We call the
> rep_1,rep_2,rep_3. The GWAS signials were under 1e-5, but the MTAG
signials
> for rep_1 was under 1e-100, rep_2 and rep_3 were under 1e-5 that same as
> the GWAS results. My question are 1) Is MATG suitable for improving the
> detection ability of duplicate data？If so, Is rep_1 an abnormal result
and
> how to handle it？
>
> Thank you very much!
>
> Tian
>
> —
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2024/05/14/03:05:46 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
<>
<> MTAG: Multi-trait Analysis of GWAS
<> Version: 1.0.8
<> (C) 2017 Omeed Maghzian, Raymond Walters, and Patrick Turley
<> Harvard University Department of Economics / Broad Institute of MIT and
Harvard
<> GNU General Public License v3
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
<> Note: It is recommended to run your own QC on the input before using
this program.
<> Software-related correspondence: ***@***.***
<> All other correspondence: ***@***.***
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
Calling ./mtag.py \
--force \
--stream-stdout \
--ld-ref-panel /data/ttian/08-GWAS_1223/01_Emmax_1223/5M_Q_K/LDscores/ \
--sumstats phen_20_PG_tbn.txt.m.ps,phen_21_PG_tbn.txt.m.ps,
phen_22_PG_tbn.txt.m.ps \
--out PG/phen_PG_tbn
#phen_20_PG_tbn(rep_1),phen_21_PG_tbn(rep_2),phen_22_PG_tbn(rep_3)
2024/05/14/03:05:46 PM Beginning MTAG analysis...
2024/05/14/03:05:46 PM MTAG will use the Z column for analyses.
2024/05/14/03:05:55 PM Read in Trait 1 summary statistics (5593073 SNPs)
from phen_20_PG_tbn.txt.m.ps ...
2024/05/14/03:05:55 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:05:55 PM Munging Trait 1
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
2024/05/14/03:05:55 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:05:55 PM Interpreting column names as follows:
2024/05/14/03:05:55 PM snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
2024/05/14/03:05:55 PM Reading sumstats from provided DataFrame into
memory 10000000 SNPs at a time.
2024/05/14/03:06:04 PM Read 5593073 SNPs from --sumstats file.
Removed 0 SNPs with missing values.
Removed 0 SNPs with INFO <= None.
Removed 0 SNPs with MAF <= 0.01.
Removed 0 SNPs with SE <0 or NaN values.
Removed 0 SNPs with out-of-bounds p-values.
Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
were not dropped.
5099629 SNPs remain.
2024/05/14/03:06:08 PM Removed 0 SNPs with duplicated rs numbers (5099629
SNPs remain).
2024/05/14/03:06:09 PM Removed 0 SNPs with N < 815.333333333 (5099629 SNPs
remain).
2024/05/14/03:06:22 PM Median value of SIGNED_SUMSTAT was 0.000275905,
which seems sensible.
2024/05/14/03:06:22 PM Dropping snps with null values
2024/05/14/03:06:22 PM
Metadata:
2024/05/14/03:06:23 PM Mean chi^2 = 0.941
2024/05/14/03:06:23 PM WARNING: mean chi^2 may be too small.
2024/05/14/03:06:23 PM Lambda GC = 0.912
2024/05/14/03:06:23 PM Max chi^2 = 30.569
2024/05/14/03:06:23 PM 1 Genome-wide significant SNPs (some may have been
removed by filtering).
2024/05/14/03:06:23 PM
Conversion finished at Tue May 14 15:06:23 2024
2024/05/14/03:06:23 PM Total time elapsed: 28.06s
2024/05/14/03:06:33 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:33 PM Munging of Trait 1 complete. SNPs remaining: 5099629
2024/05/14/03:06:33 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:33 PM Warning: The mean chi2 statistic of trait 1 is less
1.02 - MTAG estimates may be unstable.
2024/05/14/03:06:51 PM Read in Trait 2 summary statistics (5593073 SNPs)
from phen_21_PG_tbn.txt.m.ps ...
2024/05/14/03:06:51 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:51 PM Munging Trait 2
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
2024/05/14/03:06:51 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:06:51 PM Interpreting column names as follows:
2024/05/14/03:06:51 PM snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
2024/05/14/03:06:51 PM Reading sumstats from provided DataFrame into
memory 10000000 SNPs at a time.
2024/05/14/03:07:00 PM Read 5593073 SNPs from --sumstats file.
Removed 0 SNPs with missing values.
Removed 0 SNPs with INFO <= None.
Removed 0 SNPs with MAF <= 0.01.
Removed 0 SNPs with SE <0 or NaN values.
Removed 0 SNPs with out-of-bounds p-values.
Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
were not dropped.
5099629 SNPs remain.
2024/05/14/03:07:03 PM Removed 0 SNPs with duplicated rs numbers (5099629
SNPs remain).
2024/05/14/03:07:04 PM Removed 0 SNPs with N < 815.333333333 (5099629 SNPs
remain).
2024/05/14/03:07:18 PM Median value of SIGNED_SUMSTAT was 0.0122005, which
seems sensible.
2024/05/14/03:07:18 PM Dropping snps with null values
2024/05/14/03:07:18 PM
Metadata:
2024/05/14/03:07:19 PM Mean chi^2 = 0.933
2024/05/14/03:07:19 PM WARNING: mean chi^2 may be too small.
2024/05/14/03:07:19 PM Lambda GC = 0.91
2024/05/14/03:07:19 PM Max chi^2 = 25.301
2024/05/14/03:07:19 PM 0 Genome-wide significant SNPs (some may have been
removed by filtering).
2024/05/14/03:07:19 PM
Conversion finished at Tue May 14 15:07:19 2024
2024/05/14/03:07:19 PM Total time elapsed: 28.61s
2024/05/14/03:07:28 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:28 PM Munging of Trait 2 complete. SNPs remaining: 5099629
2024/05/14/03:07:28 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:28 PM Warning: The mean chi2 statistic of trait 2 is less
1.02 - MTAG estimates may be unstable.
2024/05/14/03:07:47 PM Read in Trait 3 summary statistics (5593073 SNPs)
from phen_22_PG_tbn.txt.m.ps ...
2024/05/14/03:07:47 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:47 PM Munging Trait 3
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
2024/05/14/03:07:47 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:07:47 PM Interpreting column names as follows:
2024/05/14/03:07:47 PM snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
2024/05/14/03:07:47 PM Reading sumstats from provided DataFrame into
memory 10000000 SNPs at a time.
2024/05/14/03:07:58 PM Read 5593073 SNPs from --sumstats file.
Removed 0 SNPs with missing values.
Removed 0 SNPs with INFO <= None.
Removed 0 SNPs with MAF <= 0.01.
Removed 0 SNPs with SE <0 or NaN values.
Removed 0 SNPs with out-of-bounds p-values.
Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
were not dropped.
5099629 SNPs remain.
2024/05/14/03:08:02 PM Removed 0 SNPs with duplicated rs numbers (5099629
SNPs remain).
2024/05/14/03:08:03 PM Removed 0 SNPs with N < 815.333333333 (5099629 SNPs
remain).
2024/05/14/03:08:16 PM Median value of SIGNED_SUMSTAT was 0.00952361,
which seems sensible.
2024/05/14/03:08:17 PM Dropping snps with null values
2024/05/14/03:08:17 PM
Metadata:
2024/05/14/03:08:18 PM Mean chi^2 = 0.951
2024/05/14/03:08:18 PM WARNING: mean chi^2 may be too small.
2024/05/14/03:08:18 PM Lambda GC = 0.934
2024/05/14/03:08:18 PM Max chi^2 = 31.856
2024/05/14/03:08:18 PM 3 Genome-wide significant SNPs (some may have been
removed by filtering).
2024/05/14/03:08:18 PM
Conversion finished at Tue May 14 15:08:18 2024
2024/05/14/03:08:18 PM Total time elapsed: 31.07s
2024/05/14/03:08:29 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:08:29 PM Munging of Trait 3 complete. SNPs remaining: 5099629
2024/05/14/03:08:29 PM
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
2024/05/14/03:08:30 PM Warning: The mean chi2 statistic of trait 3 is less
1.02 - MTAG estimates may be unstable.
2024/05/14/03:08:46 PM Dropped 737230 SNPs due to strand ambiguity,
4362399 SNPs remain in intersection after merging trait1
2024/05/14/03:09:03 PM Dropped 0 SNPs due to strand ambiguity, 4362399
SNPs remain in intersection after merging trait2
2024/05/14/03:09:22 PM Dropped 0 SNPs due to strand ambiguity, 4362399
SNPs remain in intersection after merging trait3
2024/05/14/03:09:22 PM ... Merge of GWAS summary statistics complete.
Number of SNPs: 4362399
2024/05/14/03:09:38 PM Using 4362399 SNPs to estimate Omega (0 SNPs
excluded due to strand ambiguity)
2024/05/14/03:09:38 PM Estimating sigma..
2024/05/14/03:14:29 PM Checking for positive definiteness ..
2024/05/14/03:14:29 PM Sigma hat:
[[1.165 0.97 0.88 ]
[0.97 1.177 0.914]
[0.88 0.914 1.131]]
2024/05/14/03:14:29 PM Mean chi^2 of SNPs used to estimate Omega is low
for some SNPsMTAG may not perform well in this situation.
2024/05/14/03:14:30 PM Beginning estimation of Omega ...
2024/05/14/03:14:30 PM Using GMM estimator of Omega ..
2024/05/14/03:14:31 PM Checking for positive definiteness ..
2024/05/14/03:14:31 PM matrix is not positive definite, performing
adjustment..
2024/05/14/03:14:31 PM Warning: max number of iterations reached in
adjustment procedure. Sigma matrix used is still non-positive-definite.
2024/05/14/03:14:31 PM Completed estimation of Omega ...
2024/05/14/03:14:31 PM Beginning MTAG calculations...
2024/05/14/03:15:19 PM ... Completed MTAG calculations.
2024/05/14/03:15:19 PM Writing Phenotype 1 to file ...
2024/05/14/03:15:58 PM Writing Phenotype 2 to file ...
2024/05/14/03:16:35 PM Writing Phenotype 3 to file ...
2024/05/14/03:17:15 PM
Summary of MTAG results:
------------------------
Trait # SNPs used N (max) N (mean) GWAS mean chi^2 MTAG mean chi^2 GWAS
equiv. (max) N
1 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.807 18.926 -113599
2 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.792 1.771 -4537
3 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.841 1.444 -3409
Estimated Omega:
[[-1.839e-04 -6.803e-09 -5.303e-09]
[-6.803e-09 -2.001e-04 -5.786e-09]
[-5.303e-09 -5.786e-09 -1.472e-04]]
(Correlation):
[[nan nan nan]
[nan nan nan]
[nan nan nan]]
Estimated Sigma:
[[1.165 0.97 0.88 ]
[0.97 1.177 0.914]
[0.88 0.914 1.131]]
(Correlation):
[[1. 0.828 0.767]
[0.828 1. 0.792]
[0.767 0.792 1. ]]
MTAG weight factors: (average across SNPs)
[-0.014 -0.035 0.061]
2024/05/14/03:17:15 PM
2024/05/14/03:17:15 PM MTAG results saved to file.
2024/05/14/03:17:15 PM MTAG complete. Time elapsed: 11.0m:29.370085001s
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Mean chi2 is both a function of heritability and sample size. Your sample
size must be quite small then.
…On Wed, May 22, 2024, 5:27 AM real ***@***.***> wrote:
Hello Patrick
Thanks for your reply. I find that the mean chr^2 of my GWAS results for
all the traits were less than 1. My phenotype data includes plant height,
leaf angle and tassel branch numbers, etc which have higher broad sense
heritability.Where could this be the problems?
Thank you and all the best,
Tian
At 2024-05-22 04:40:51, "paturley" ***@***.***> wrote:
Ah. So the problem is that your mean chi2 statistics are less than one, so
the implicit heritability is negative. I generally recommend that MTAG not
be used unless the mean chi2 is at least 1.1 for each trait. Better if it's
even higher than that. In your particular case, I think MTAG may not be the
right tool.
On Mon, May 20, 2024 at 9:53 PM real ***@***.***> wrote:
> Hello Patrick
>
>
>
>
> Thanks for your reply. Yes, I think the results for rep_1 is spurious.
The
> Manhattan plots for GWAS and MATG as well as the log file were attatched.
>
>
>
>
> Thank you very much!
>
>
>
>
> Best,
>
>
>
>
> Tian
>
>
>
>
>
>
>
>
>
>
> At 2024-05-21 02:41:50, "paturley" ***@***.***> wrote:
>
> Hello Tian,
>
> I'm a bit confused by your question. Are you worried that the very
> significant results for rep_1 is spurious? If you post your log file, it
> will help me understand what is going on better.
>
> Best,
> Patrick
>
> On Mon, May 20, 2024 at 4:06 AM real ***@***.***> wrote:
>
> > Hello,
> >
> > I used MTAG to enhance the GWAS ability. I have phenotypic data of
three
> > environments of plant hegiht which has low repeatability. We call the
> > rep_1,rep_2,rep_3. The GWAS signials were under 1e-5, but the MTAG
> signials
> > for rep_1 was under 1e-100, rep_2 and rep_3 were under 1e-5 that same
as
> > the GWAS results. My question are 1) Is MATG suitable for improving the
> > detection ability of duplicate data？If so, Is rep_1 an abnormal result
> and
> > how to handle it？
> >
> > Thank you very much!
> >
> > Tian
> >
> > —
> > Reply to this email directly, view it on GitHub
> > <#213>, or unsubscribe
> > <
>
https://github.com/notifications/unsubscribe-auth/AFBUB5LNIGHOATZ7YCQTGRLZDGVHZAVCNFSM6AAAAABH7H4OY2VHI2DSMVQWIX3LMV43ASLTON2WKOZSGMYDKMZYGM4DSMI
> >
> > .
> > You are receiving this because you are subscribed to this
thread.Message
> > ID: ***@***.***>
> >
>
>
> —
> Reply to this email directly, view it on GitHub, or unsubscribe.
> You are receiving this because you authored the thread.Message ID:
> ***@***.***>
> 2024/05/14/03:05:46 PM
>
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> <>
> <> MTAG: Multi-trait Analysis of GWAS
> <> Version: 1.0.8
> <> (C) 2017 Omeed Maghzian, Raymond Walters, and Patrick Turley
> <> Harvard University Department of Economics / Broad Institute of MIT
and
> Harvard
> <> GNU General Public License v3
>
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> <> Note: It is recommended to run your own QC on the input before using
> this program.
> <> Software-related correspondence: ***@***.***
> <> All other correspondence: ***@***.***
>
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
>
>
> Calling ./mtag.py \
> --force \
> --stream-stdout \
> --ld-ref-panel /data/ttian/08-GWAS_1223/01_Emmax_1223/5M_Q_K/LDscores/ \
> --sumstats phen_20_PG_tbn.txt.m.ps,phen_21_PG_tbn.txt.m.ps,
> phen_22_PG_tbn.txt.m.ps \
> --out PG/phen_PG_tbn
>
> #phen_20_PG_tbn(rep_1),phen_21_PG_tbn(rep_2),phen_22_PG_tbn(rep_3)
>
> 2024/05/14/03:05:46 PM Beginning MTAG analysis...
> 2024/05/14/03:05:46 PM MTAG will use the Z column for analyses.
> 2024/05/14/03:05:55 PM Read in Trait 1 summary statistics (5593073 SNPs)
> from phen_20_PG_tbn.txt.m.ps ...
> 2024/05/14/03:05:55 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:05:55 PM Munging Trait 1
> <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> 2024/05/14/03:05:55 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:05:55 PM Interpreting column names as follows:
> 2024/05/14/03:05:55 PM snpid: Variant ID (e.g., rs number)
> n: Sample size
> a1: a1, interpreted as ref allele for signed sumstat.
> pval: p-Value
> a2: a2, interpreted as non-ref allele for signed sumstat.
> z: Directional summary statistic as specified by --signed-sumstats.
>
> 2024/05/14/03:05:55 PM Reading sumstats from provided DataFrame into
> memory 10000000 SNPs at a time.
> 2024/05/14/03:06:04 PM Read 5593073 SNPs from --sumstats file.
> Removed 0 SNPs with missing values.
> Removed 0 SNPs with INFO <= None.
> Removed 0 SNPs with MAF <= 0.01.
> Removed 0 SNPs with SE <0 or NaN values.
> Removed 0 SNPs with out-of-bounds p-values.
> Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
> were not dropped.
> 5099629 SNPs remain.
> 2024/05/14/03:06:08 PM Removed 0 SNPs with duplicated rs numbers (5099629
> SNPs remain).
> 2024/05/14/03:06:09 PM Removed 0 SNPs with N < 815.333333333 (5099629
SNPs
> remain).
> 2024/05/14/03:06:22 PM Median value of SIGNED_SUMSTAT was 0.000275905,
> which seems sensible.
> 2024/05/14/03:06:22 PM Dropping snps with null values
> 2024/05/14/03:06:22 PM
> Metadata:
> 2024/05/14/03:06:23 PM Mean chi^2 = 0.941
> 2024/05/14/03:06:23 PM WARNING: mean chi^2 may be too small.
> 2024/05/14/03:06:23 PM Lambda GC = 0.912
> 2024/05/14/03:06:23 PM Max chi^2 = 30.569
> 2024/05/14/03:06:23 PM 1 Genome-wide significant SNPs (some may have been
> removed by filtering).
> 2024/05/14/03:06:23 PM
> Conversion finished at Tue May 14 15:06:23 2024
> 2024/05/14/03:06:23 PM Total time elapsed: 28.06s
> 2024/05/14/03:06:33 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:06:33 PM Munging of Trait 1 complete. SNPs remaining:
5099629
> 2024/05/14/03:06:33 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
>
> 2024/05/14/03:06:33 PM Warning: The mean chi2 statistic of trait 1 is
less
> 1.02 - MTAG estimates may be unstable.
> 2024/05/14/03:06:51 PM Read in Trait 2 summary statistics (5593073 SNPs)
> from phen_21_PG_tbn.txt.m.ps ...
> 2024/05/14/03:06:51 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:06:51 PM Munging Trait 2
> <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> 2024/05/14/03:06:51 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:06:51 PM Interpreting column names as follows:
> 2024/05/14/03:06:51 PM snpid: Variant ID (e.g., rs number)
> n: Sample size
> a1: a1, interpreted as ref allele for signed sumstat.
> pval: p-Value
> a2: a2, interpreted as non-ref allele for signed sumstat.
> z: Directional summary statistic as specified by --signed-sumstats.
>
> 2024/05/14/03:06:51 PM Reading sumstats from provided DataFrame into
> memory 10000000 SNPs at a time.
> 2024/05/14/03:07:00 PM Read 5593073 SNPs from --sumstats file.
> Removed 0 SNPs with missing values.
> Removed 0 SNPs with INFO <= None.
> Removed 0 SNPs with MAF <= 0.01.
> Removed 0 SNPs with SE <0 or NaN values.
> Removed 0 SNPs with out-of-bounds p-values.
> Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
> were not dropped.
> 5099629 SNPs remain.
> 2024/05/14/03:07:03 PM Removed 0 SNPs with duplicated rs numbers (5099629
> SNPs remain).
> 2024/05/14/03:07:04 PM Removed 0 SNPs with N < 815.333333333 (5099629
SNPs
> remain).
> 2024/05/14/03:07:18 PM Median value of SIGNED_SUMSTAT was 0.0122005,
which
> seems sensible.
> 2024/05/14/03:07:18 PM Dropping snps with null values
> 2024/05/14/03:07:18 PM
> Metadata:
> 2024/05/14/03:07:19 PM Mean chi^2 = 0.933
> 2024/05/14/03:07:19 PM WARNING: mean chi^2 may be too small.
> 2024/05/14/03:07:19 PM Lambda GC = 0.91
> 2024/05/14/03:07:19 PM Max chi^2 = 25.301
> 2024/05/14/03:07:19 PM 0 Genome-wide significant SNPs (some may have been
> removed by filtering).
> 2024/05/14/03:07:19 PM
> Conversion finished at Tue May 14 15:07:19 2024
> 2024/05/14/03:07:19 PM Total time elapsed: 28.61s
> 2024/05/14/03:07:28 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:07:28 PM Munging of Trait 2 complete. SNPs remaining:
5099629
> 2024/05/14/03:07:28 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
>
> 2024/05/14/03:07:28 PM Warning: The mean chi2 statistic of trait 2 is
less
> 1.02 - MTAG estimates may be unstable.
> 2024/05/14/03:07:47 PM Read in Trait 3 summary statistics (5593073 SNPs)
> from phen_22_PG_tbn.txt.m.ps ...
> 2024/05/14/03:07:47 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:07:47 PM Munging Trait 3
> <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> 2024/05/14/03:07:47 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:07:47 PM Interpreting column names as follows:
> 2024/05/14/03:07:47 PM snpid: Variant ID (e.g., rs number)
> n: Sample size
> a1: a1, interpreted as ref allele for signed sumstat.
> pval: p-Value
> a2: a2, interpreted as non-ref allele for signed sumstat.
> z: Directional summary statistic as specified by --signed-sumstats.
>
> 2024/05/14/03:07:47 PM Reading sumstats from provided DataFrame into
> memory 10000000 SNPs at a time.
> 2024/05/14/03:07:58 PM Read 5593073 SNPs from --sumstats file.
> Removed 0 SNPs with missing values.
> Removed 0 SNPs with INFO <= None.
> Removed 0 SNPs with MAF <= 0.01.
> Removed 0 SNPs with SE <0 or NaN values.
> Removed 0 SNPs with out-of-bounds p-values.
> Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
> were not dropped.
> 5099629 SNPs remain.
> 2024/05/14/03:08:02 PM Removed 0 SNPs with duplicated rs numbers (5099629
> SNPs remain).
> 2024/05/14/03:08:03 PM Removed 0 SNPs with N < 815.333333333 (5099629
SNPs
> remain).
> 2024/05/14/03:08:16 PM Median value of SIGNED_SUMSTAT was 0.00952361,
> which seems sensible.
> 2024/05/14/03:08:17 PM Dropping snps with null values
> 2024/05/14/03:08:17 PM
> Metadata:
> 2024/05/14/03:08:18 PM Mean chi^2 = 0.951
> 2024/05/14/03:08:18 PM WARNING: mean chi^2 may be too small.
> 2024/05/14/03:08:18 PM Lambda GC = 0.934
> 2024/05/14/03:08:18 PM Max chi^2 = 31.856
> 2024/05/14/03:08:18 PM 3 Genome-wide significant SNPs (some may have been
> removed by filtering).
> 2024/05/14/03:08:18 PM
> Conversion finished at Tue May 14 15:08:18 2024
> 2024/05/14/03:08:18 PM Total time elapsed: 31.07s
> 2024/05/14/03:08:29 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:08:29 PM Munging of Trait 3 complete. SNPs remaining:
5099629
> 2024/05/14/03:08:29 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
>
> 2024/05/14/03:08:30 PM Warning: The mean chi2 statistic of trait 3 is
less
> 1.02 - MTAG estimates may be unstable.
> 2024/05/14/03:08:46 PM Dropped 737230 SNPs due to strand ambiguity,
> 4362399 SNPs remain in intersection after merging trait1
> 2024/05/14/03:09:03 PM Dropped 0 SNPs due to strand ambiguity, 4362399
> SNPs remain in intersection after merging trait2
> 2024/05/14/03:09:22 PM Dropped 0 SNPs due to strand ambiguity, 4362399
> SNPs remain in intersection after merging trait3
> 2024/05/14/03:09:22 PM ... Merge of GWAS summary statistics complete.
> Number of SNPs: 4362399
> 2024/05/14/03:09:38 PM Using 4362399 SNPs to estimate Omega (0 SNPs
> excluded due to strand ambiguity)
> 2024/05/14/03:09:38 PM Estimating sigma..
> 2024/05/14/03:14:29 PM Checking for positive definiteness ..
> 2024/05/14/03:14:29 PM Sigma hat:
> [[1.165 0.97 0.88 ]
> [0.97 1.177 0.914]
> [0.88 0.914 1.131]]
> 2024/05/14/03:14:29 PM Mean chi^2 of SNPs used to estimate Omega is low
> for some SNPsMTAG may not perform well in this situation.
> 2024/05/14/03:14:30 PM Beginning estimation of Omega ...
> 2024/05/14/03:14:30 PM Using GMM estimator of Omega ..
> 2024/05/14/03:14:31 PM Checking for positive definiteness ..
> 2024/05/14/03:14:31 PM matrix is not positive definite, performing
> adjustment..
> 2024/05/14/03:14:31 PM Warning: max number of iterations reached in
> adjustment procedure. Sigma matrix used is still non-positive-definite.
> 2024/05/14/03:14:31 PM Completed estimation of Omega ...
> 2024/05/14/03:14:31 PM Beginning MTAG calculations...
> 2024/05/14/03:15:19 PM ... Completed MTAG calculations.
> 2024/05/14/03:15:19 PM Writing Phenotype 1 to file ...
> 2024/05/14/03:15:58 PM Writing Phenotype 2 to file ...
> 2024/05/14/03:16:35 PM Writing Phenotype 3 to file ...
> 2024/05/14/03:17:15 PM
> Summary of MTAG results:
> ------------------------
> Trait # SNPs used N (max) N (mean) GWAS mean chi^2 MTAG mean chi^2 GWAS
> equiv. (max) N
> 1 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.807 18.926 -113599
> 2 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.792 1.771 -4537
> 3 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.841 1.444 -3409
>
> Estimated Omega:
> [[-1.839e-04 -6.803e-09 -5.303e-09]
> [-6.803e-09 -2.001e-04 -5.786e-09]
> [-5.303e-09 -5.786e-09 -1.472e-04]]
>
> (Correlation):
> [[nan nan nan]
> [nan nan nan]
> [nan nan nan]]
>
> Estimated Sigma:
> [[1.165 0.97 0.88 ]
> [0.97 1.177 0.914]
> [0.88 0.914 1.131]]
>
> (Correlation):
> [[1. 0.828 0.767]
> [0.828 1. 0.792]
> [0.767 0.792 1. ]]
>
> MTAG weight factors: (average across SNPs)
> [-0.014 -0.035 0.061]
>
> 2024/05/14/03:17:15 PM
> 2024/05/14/03:17:15 PM MTAG results saved to file.
> 2024/05/14/03:17:15 PM MTAG complete. Time elapsed: 11.0m:29.370085001s
>
> —
> Reply to this email directly, view it on GitHub
> <#213 (comment)>, or
> unsubscribe
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>
> .
> You are receiving this because you commented.Message ID:
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I have more than 1000 samples which are relatively large for maize population.Is there other problems？Thank youTian在 2024年5月22日，18:49，paturley ***@***.***> 写道：
Mean chi2 is both a function of heritability and sample size. Your sample
size must be quite small then.
On Wed, May 22, 2024, 5:27 AM real ***@***.***> wrote:
Hello Patrick
Thanks for your reply. I find that the mean chr^2 of my GWAS results for
all the traits were less than 1. My phenotype data includes plant height,
leaf angle and tassel branch numbers, etc which have higher broad sense
heritability.Where could this be the problems?
Thank you and all the best,
Tian
At 2024-05-22 04:40:51, "paturley" ***@***.***> wrote:
Ah. So the problem is that your mean chi2 statistics are less than one, so
the implicit heritability is negative. I generally recommend that MTAG not
be used unless the mean chi2 is at least 1.1 for each trait. Better if it's
even higher than that. In your particular case, I think MTAG may not be the
right tool.
On Mon, May 20, 2024 at 9:53 PM real ***@***.***> wrote:
> Hello Patrick
>
>
>
>
> Thanks for your reply. Yes, I think the results for rep_1 is spurious.
The
> Manhattan plots for GWAS and MATG as well as the log file were attatched.
>
>
>
>
> Thank you very much!
>
>
>
>
> Best,
>
>
>
>
> Tian
>
>
>
>
>
>
>
>
>
>
> At 2024-05-21 02:41:50, "paturley" ***@***.***> wrote:
>
> Hello Tian,
>
> I'm a bit confused by your question. Are you worried that the very
> significant results for rep_1 is spurious? If you post your log file, it
> will help me understand what is going on better.
>
> Best,
> Patrick
>
> On Mon, May 20, 2024 at 4:06 AM real ***@***.***> wrote:
>
> > Hello,
> >
> > I used MTAG to enhance the GWAS ability. I have phenotypic data of
three
> > environments of plant hegiht which has low repeatability. We call the
> > rep_1,rep_2,rep_3. The GWAS signials were under 1e-5, but the MTAG
> signials
> > for rep_1 was under 1e-100, rep_2 and rep_3 were under 1e-5 that same
as
> > the GWAS results. My question are 1) Is MATG suitable for improving the
> > detection ability of duplicate data？If so, Is rep_1 an abnormal result
> and
> > how to handle it？
> >
> > Thank you very much!
> >
> > Tian
> >
> > —
> > Reply to this email directly, view it on GitHub
> > <#213>, or unsubscribe
> > <
>
https://github.com/notifications/unsubscribe-auth/AFBUB5LNIGHOATZ7YCQTGRLZDGVHZAVCNFSM6AAAAABH7H4OY2VHI2DSMVQWIX3LMV43ASLTON2WKOZSGMYDKMZYGM4DSMI
> >
> > .
> > You are receiving this because you are subscribed to this
thread.Message
> > ID: ***@***.***>
> >
>
>
> —
> Reply to this email directly, view it on GitHub, or unsubscribe.
> You are receiving this because you authored the thread.Message ID:
> ***@***.***>
> 2024/05/14/03:05:46 PM
>
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> <>
> <> MTAG: Multi-trait Analysis of GWAS
> <> Version: 1.0.8
> <> (C) 2017 Omeed Maghzian, Raymond Walters, and Patrick Turley
> <> Harvard University Department of Economics / Broad Institute of MIT
and
> Harvard
> <> GNU General Public License v3
>
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> <> Note: It is recommended to run your own QC on the input before using
> this program.
> <> Software-related correspondence: ***@***.***
> <> All other correspondence: ***@***.***
>
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
>
>
> Calling ./mtag.py \
> --force \
> --stream-stdout \
> --ld-ref-panel /data/ttian/08-GWAS_1223/01_Emmax_1223/5M_Q_K/LDscores/ \
> --sumstats phen_20_PG_tbn.txt.m.ps,phen_21_PG_tbn.txt.m.ps,
> phen_22_PG_tbn.txt.m.ps \
> --out PG/phen_PG_tbn
>
> #phen_20_PG_tbn(rep_1),phen_21_PG_tbn(rep_2),phen_22_PG_tbn(rep_3)
>
> 2024/05/14/03:05:46 PM Beginning MTAG analysis...
> 2024/05/14/03:05:46 PM MTAG will use the Z column for analyses.
> 2024/05/14/03:05:55 PM Read in Trait 1 summary statistics (5593073 SNPs)
> from phen_20_PG_tbn.txt.m.ps ...
> 2024/05/14/03:05:55 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:05:55 PM Munging Trait 1
> <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> 2024/05/14/03:05:55 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:05:55 PM Interpreting column names as follows:
> 2024/05/14/03:05:55 PM snpid: Variant ID (e.g., rs number)
> n: Sample size
> a1: a1, interpreted as ref allele for signed sumstat.
> pval: p-Value
> a2: a2, interpreted as non-ref allele for signed sumstat.
> z: Directional summary statistic as specified by --signed-sumstats.
>
> 2024/05/14/03:05:55 PM Reading sumstats from provided DataFrame into
> memory 10000000 SNPs at a time.
> 2024/05/14/03:06:04 PM Read 5593073 SNPs from --sumstats file.
> Removed 0 SNPs with missing values.
> Removed 0 SNPs with INFO <= None.
> Removed 0 SNPs with MAF <= 0.01.
> Removed 0 SNPs with SE <0 or NaN values.
> Removed 0 SNPs with out-of-bounds p-values.
> Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
> were not dropped.
> 5099629 SNPs remain.
> 2024/05/14/03:06:08 PM Removed 0 SNPs with duplicated rs numbers (5099629
> SNPs remain).
> 2024/05/14/03:06:09 PM Removed 0 SNPs with N < 815.333333333 (5099629
SNPs
> remain).
> 2024/05/14/03:06:22 PM Median value of SIGNED_SUMSTAT was 0.000275905,
> which seems sensible.
> 2024/05/14/03:06:22 PM Dropping snps with null values
> 2024/05/14/03:06:22 PM
> Metadata:
> 2024/05/14/03:06:23 PM Mean chi^2 = 0.941
> 2024/05/14/03:06:23 PM WARNING: mean chi^2 may be too small.
> 2024/05/14/03:06:23 PM Lambda GC = 0.912
> 2024/05/14/03:06:23 PM Max chi^2 = 30.569
> 2024/05/14/03:06:23 PM 1 Genome-wide significant SNPs (some may have been
> removed by filtering).
> 2024/05/14/03:06:23 PM
> Conversion finished at Tue May 14 15:06:23 2024
> 2024/05/14/03:06:23 PM Total time elapsed: 28.06s
> 2024/05/14/03:06:33 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:06:33 PM Munging of Trait 1 complete. SNPs remaining:
5099629
> 2024/05/14/03:06:33 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
>
> 2024/05/14/03:06:33 PM Warning: The mean chi2 statistic of trait 1 is
less
> 1.02 - MTAG estimates may be unstable.
> 2024/05/14/03:06:51 PM Read in Trait 2 summary statistics (5593073 SNPs)
> from phen_21_PG_tbn.txt.m.ps ...
> 2024/05/14/03:06:51 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:06:51 PM Munging Trait 2
> <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> 2024/05/14/03:06:51 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:06:51 PM Interpreting column names as follows:
> 2024/05/14/03:06:51 PM snpid: Variant ID (e.g., rs number)
> n: Sample size
> a1: a1, interpreted as ref allele for signed sumstat.
> pval: p-Value
> a2: a2, interpreted as non-ref allele for signed sumstat.
> z: Directional summary statistic as specified by --signed-sumstats.
>
> 2024/05/14/03:06:51 PM Reading sumstats from provided DataFrame into
> memory 10000000 SNPs at a time.
> 2024/05/14/03:07:00 PM Read 5593073 SNPs from --sumstats file.
> Removed 0 SNPs with missing values.
> Removed 0 SNPs with INFO <= None.
> Removed 0 SNPs with MAF <= 0.01.
> Removed 0 SNPs with SE <0 or NaN values.
> Removed 0 SNPs with out-of-bounds p-values.
> Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
> were not dropped.
> 5099629 SNPs remain.
> 2024/05/14/03:07:03 PM Removed 0 SNPs with duplicated rs numbers (5099629
> SNPs remain).
> 2024/05/14/03:07:04 PM Removed 0 SNPs with N < 815.333333333 (5099629
SNPs
> remain).
> 2024/05/14/03:07:18 PM Median value of SIGNED_SUMSTAT was 0.0122005,
which
> seems sensible.
> 2024/05/14/03:07:18 PM Dropping snps with null values
> 2024/05/14/03:07:18 PM
> Metadata:
> 2024/05/14/03:07:19 PM Mean chi^2 = 0.933
> 2024/05/14/03:07:19 PM WARNING: mean chi^2 may be too small.
> 2024/05/14/03:07:19 PM Lambda GC = 0.91
> 2024/05/14/03:07:19 PM Max chi^2 = 25.301
> 2024/05/14/03:07:19 PM 0 Genome-wide significant SNPs (some may have been
> removed by filtering).
> 2024/05/14/03:07:19 PM
> Conversion finished at Tue May 14 15:07:19 2024
> 2024/05/14/03:07:19 PM Total time elapsed: 28.61s
> 2024/05/14/03:07:28 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:07:28 PM Munging of Trait 2 complete. SNPs remaining:
5099629
> 2024/05/14/03:07:28 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
>
> 2024/05/14/03:07:28 PM Warning: The mean chi2 statistic of trait 2 is
less
> 1.02 - MTAG estimates may be unstable.
> 2024/05/14/03:07:47 PM Read in Trait 3 summary statistics (5593073 SNPs)
> from phen_22_PG_tbn.txt.m.ps ...
> 2024/05/14/03:07:47 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:07:47 PM Munging Trait 3
> <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> 2024/05/14/03:07:47 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:07:47 PM Interpreting column names as follows:
> 2024/05/14/03:07:47 PM snpid: Variant ID (e.g., rs number)
> n: Sample size
> a1: a1, interpreted as ref allele for signed sumstat.
> pval: p-Value
> a2: a2, interpreted as non-ref allele for signed sumstat.
> z: Directional summary statistic as specified by --signed-sumstats.
>
> 2024/05/14/03:07:47 PM Reading sumstats from provided DataFrame into
> memory 10000000 SNPs at a time.
> 2024/05/14/03:07:58 PM Read 5593073 SNPs from --sumstats file.
> Removed 0 SNPs with missing values.
> Removed 0 SNPs with INFO <= None.
> Removed 0 SNPs with MAF <= 0.01.
> Removed 0 SNPs with SE <0 or NaN values.
> Removed 0 SNPs with out-of-bounds p-values.
> Removed 493444 variants that were not SNPs. Note: strand ambiguous SNPs
> were not dropped.
> 5099629 SNPs remain.
> 2024/05/14/03:08:02 PM Removed 0 SNPs with duplicated rs numbers (5099629
> SNPs remain).
> 2024/05/14/03:08:03 PM Removed 0 SNPs with N < 815.333333333 (5099629
SNPs
> remain).
> 2024/05/14/03:08:16 PM Median value of SIGNED_SUMSTAT was 0.00952361,
> which seems sensible.
> 2024/05/14/03:08:17 PM Dropping snps with null values
> 2024/05/14/03:08:17 PM
> Metadata:
> 2024/05/14/03:08:18 PM Mean chi^2 = 0.951
> 2024/05/14/03:08:18 PM WARNING: mean chi^2 may be too small.
> 2024/05/14/03:08:18 PM Lambda GC = 0.934
> 2024/05/14/03:08:18 PM Max chi^2 = 31.856
> 2024/05/14/03:08:18 PM 3 Genome-wide significant SNPs (some may have been
> removed by filtering).
> 2024/05/14/03:08:18 PM
> Conversion finished at Tue May 14 15:08:18 2024
> 2024/05/14/03:08:18 PM Total time elapsed: 31.07s
> 2024/05/14/03:08:29 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> 2024/05/14/03:08:29 PM Munging of Trait 3 complete. SNPs remaining:
5099629
> 2024/05/14/03:08:29 PM
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
>
> 2024/05/14/03:08:30 PM Warning: The mean chi2 statistic of trait 3 is
less
> 1.02 - MTAG estimates may be unstable.
> 2024/05/14/03:08:46 PM Dropped 737230 SNPs due to strand ambiguity,
> 4362399 SNPs remain in intersection after merging trait1
> 2024/05/14/03:09:03 PM Dropped 0 SNPs due to strand ambiguity, 4362399
> SNPs remain in intersection after merging trait2
> 2024/05/14/03:09:22 PM Dropped 0 SNPs due to strand ambiguity, 4362399
> SNPs remain in intersection after merging trait3
> 2024/05/14/03:09:22 PM ... Merge of GWAS summary statistics complete.
> Number of SNPs: 4362399
> 2024/05/14/03:09:38 PM Using 4362399 SNPs to estimate Omega (0 SNPs
> excluded due to strand ambiguity)
> 2024/05/14/03:09:38 PM Estimating sigma..
> 2024/05/14/03:14:29 PM Checking for positive definiteness ..
> 2024/05/14/03:14:29 PM Sigma hat:
> [[1.165 0.97 0.88 ]
> [0.97 1.177 0.914]
> [0.88 0.914 1.131]]
> 2024/05/14/03:14:29 PM Mean chi^2 of SNPs used to estimate Omega is low
> for some SNPsMTAG may not perform well in this situation.
> 2024/05/14/03:14:30 PM Beginning estimation of Omega ...
> 2024/05/14/03:14:30 PM Using GMM estimator of Omega ..
> 2024/05/14/03:14:31 PM Checking for positive definiteness ..
> 2024/05/14/03:14:31 PM matrix is not positive definite, performing
> adjustment..
> 2024/05/14/03:14:31 PM Warning: max number of iterations reached in
> adjustment procedure. Sigma matrix used is still non-positive-definite.
> 2024/05/14/03:14:31 PM Completed estimation of Omega ...
> 2024/05/14/03:14:31 PM Beginning MTAG calculations...
> 2024/05/14/03:15:19 PM ... Completed MTAG calculations.
> 2024/05/14/03:15:19 PM Writing Phenotype 1 to file ...
> 2024/05/14/03:15:58 PM Writing Phenotype 2 to file ...
> 2024/05/14/03:16:35 PM Writing Phenotype 3 to file ...
> 2024/05/14/03:17:15 PM
> Summary of MTAG results:
> ------------------------
> Trait # SNPs used N (max) N (mean) GWAS mean chi^2 MTAG mean chi^2 GWAS
> equiv. (max) N
> 1 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.807 18.926 -113599
> 2 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.792 1.771 -4537
> 3 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.841 1.444 -3409
>
> Estimated Omega:
> [[-1.839e-04 -6.803e-09 -5.303e-09]
> [-6.803e-09 -2.001e-04 -5.786e-09]
> [-5.303e-09 -5.786e-09 -1.472e-04]]
>
> (Correlation):
> [[nan nan nan]
> [nan nan nan]
> [nan nan nan]]
>
> Estimated Sigma:
> [[1.165 0.97 0.88 ]
> [0.97 1.177 0.914]
> [0.88 0.914 1.131]]
>
> (Correlation):
> [[1. 0.828 0.767]
> [0.828 1. 0.792]
> [0.767 0.792 1. ]]
>
> MTAG weight factors: (average across SNPs)
> [-0.014 -0.035 0.061]
>
> 2024/05/14/03:17:15 PM
> 2024/05/14/03:17:15 PM MTAG results saved to file.
> 2024/05/14/03:17:15 PM MTAG complete. Time elapsed: 11.0m:29.370085001s
>
> —
> Reply to this email directly, view it on GitHub
> <#213 (comment)>, or
> unsubscribe
> <
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>
> .
> You are receiving this because you commented.Message ID:
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|
1000 may be large for maize samples, but it doesn't appear to be large
enough for MTAG, which requires mean chi2 statistics that are greater than
one. Sorry I can't be more helpful.
…On Wed, May 22, 2024, 7:02 AM real ***@***.***> wrote:
I have more than 1000 samples which are relatively large for maize
population.Is there other problems？Thank youTian在 2024年5月22日，18:49，paturley
***@***.***> 写道：
Mean chi2 is both a function of heritability and sample size. Your sample
size must be quite small then.
On Wed, May 22, 2024, 5:27 AM real ***@***.***> wrote:
> Hello Patrick
>
>
>
>
> Thanks for your reply. I find that the mean chr^2 of my GWAS results for
> all the traits were less than 1. My phenotype data includes plant
height,
> leaf angle and tassel branch numbers, etc which have higher broad sense
> heritability.Where could this be the problems?
>
>
>
>
> Thank you and all the best,
>
>
>
>
> Tian
>
>
>
>
>
>
>
>
>
>
> At 2024-05-22 04:40:51, "paturley" ***@***.***> wrote:
>
> Ah. So the problem is that your mean chi2 statistics are less than one,
so
> the implicit heritability is negative. I generally recommend that MTAG
not
> be used unless the mean chi2 is at least 1.1 for each trait. Better if
it's
> even higher than that. In your particular case, I think MTAG may not be
the
> right tool.
>
> On Mon, May 20, 2024 at 9:53 PM real ***@***.***> wrote:
>
> > Hello Patrick
> >
> >
> >
> >
> > Thanks for your reply. Yes, I think the results for rep_1 is spurious.
> The
> > Manhattan plots for GWAS and MATG as well as the log file were
attatched.
> >
> >
> >
> >
> > Thank you very much!
> >
> >
> >
> >
> > Best,
> >
> >
> >
> >
> > Tian
> >
> >
> >
> >
> >
> >
> >
> >
> >
> >
> > At 2024-05-21 02:41:50, "paturley" ***@***.***> wrote:
> >
> > Hello Tian,
> >
> > I'm a bit confused by your question. Are you worried that the very
> > significant results for rep_1 is spurious? If you post your log file,
it
> > will help me understand what is going on better.
> >
> > Best,
> > Patrick
> >
> > On Mon, May 20, 2024 at 4:06 AM real ***@***.***> wrote:
> >
> > > Hello,
> > >
> > > I used MTAG to enhance the GWAS ability. I have phenotypic data of
> three
> > > environments of plant hegiht which has low repeatability. We call
the
> > > rep_1,rep_2,rep_3. The GWAS signials were under 1e-5, but the MTAG
> > signials
> > > for rep_1 was under 1e-100, rep_2 and rep_3 were under 1e-5 that
same
> as
> > > the GWAS results. My question are 1) Is MATG suitable for improving
the
> > > detection ability of duplicate data？If so, Is rep_1 an abnormal
result
> > and
> > > how to handle it？
> > >
> > > Thank you very much!
> > >
> > > Tian
> > >
> > > —
> > > Reply to this email directly, view it on GitHub
> > > <#213>, or unsubscribe
> > > <
> >
>
https://github.com/notifications/unsubscribe-auth/AFBUB5LNIGHOATZ7YCQTGRLZDGVHZAVCNFSM6AAAAABH7H4OY2VHI2DSMVQWIX3LMV43ASLTON2WKOZSGMYDKMZYGM4DSMI
> > >
> > > .
> > > You are receiving this because you are subscribed to this
> thread.Message
> > > ID: ***@***.***>
> > >
> >
> >
> > —
> > Reply to this email directly, view it on GitHub, or unsubscribe.
> > You are receiving this because you authored the thread.Message ID:
> > ***@***.***>
> > 2024/05/14/03:05:46 PM
> >
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > <>
> > <> MTAG: Multi-trait Analysis of GWAS
> > <> Version: 1.0.8
> > <> (C) 2017 Omeed Maghzian, Raymond Walters, and Patrick Turley
> > <> Harvard University Department of Economics / Broad Institute of MIT
> and
> > Harvard
> > <> GNU General Public License v3
> >
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > <> Note: It is recommended to run your own QC on the input before
using
> > this program.
> > <> Software-related correspondence: ***@***.***
> > <> All other correspondence: ***@***.***
> >
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> >
> >
> > Calling ./mtag.py \
> > --force \
> > --stream-stdout \
> > --ld-ref-panel /data/ttian/08-GWAS_1223/01_Emmax_1223/5M_Q_K/LDscores/
\
> > --sumstats phen_20_PG_tbn.txt.m.ps,phen_21_PG_tbn.txt.m.ps,
> > phen_22_PG_tbn.txt.m.ps \
> > --out PG/phen_PG_tbn
> >
> > #phen_20_PG_tbn(rep_1),phen_21_PG_tbn(rep_2),phen_22_PG_tbn(rep_3)
> >
> > 2024/05/14/03:05:46 PM Beginning MTAG analysis...
> > 2024/05/14/03:05:46 PM MTAG will use the Z column for analyses.
> > 2024/05/14/03:05:55 PM Read in Trait 1 summary statistics (5593073
SNPs)
> > from phen_20_PG_tbn.txt.m.ps ...
> > 2024/05/14/03:05:55 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:05:55 PM Munging Trait 1
> > <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> > 2024/05/14/03:05:55 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:05:55 PM Interpreting column names as follows:
> > 2024/05/14/03:05:55 PM snpid: Variant ID (e.g., rs number)
> > n: Sample size
> > a1: a1, interpreted as ref allele for signed sumstat.
> > pval: p-Value
> > a2: a2, interpreted as non-ref allele for signed sumstat.
> > z: Directional summary statistic as specified by --signed-sumstats.
> >
> > 2024/05/14/03:05:55 PM Reading sumstats from provided DataFrame into
> > memory 10000000 SNPs at a time.
> > 2024/05/14/03:06:04 PM Read 5593073 SNPs from --sumstats file.
> > Removed 0 SNPs with missing values.
> > Removed 0 SNPs with INFO <= None.
> > Removed 0 SNPs with MAF <= 0.01.
> > Removed 0 SNPs with SE <0 or NaN values.
> > Removed 0 SNPs with out-of-bounds p-values.
> > Removed 493444 variants that were not SNPs. Note: strand ambiguous
SNPs
> > were not dropped.
> > 5099629 SNPs remain.
> > 2024/05/14/03:06:08 PM Removed 0 SNPs with duplicated rs numbers
(5099629
> > SNPs remain).
> > 2024/05/14/03:06:09 PM Removed 0 SNPs with N < 815.333333333 (5099629
> SNPs
> > remain).
> > 2024/05/14/03:06:22 PM Median value of SIGNED_SUMSTAT was 0.000275905,
> > which seems sensible.
> > 2024/05/14/03:06:22 PM Dropping snps with null values
> > 2024/05/14/03:06:22 PM
> > Metadata:
> > 2024/05/14/03:06:23 PM Mean chi^2 = 0.941
> > 2024/05/14/03:06:23 PM WARNING: mean chi^2 may be too small.
> > 2024/05/14/03:06:23 PM Lambda GC = 0.912
> > 2024/05/14/03:06:23 PM Max chi^2 = 30.569
> > 2024/05/14/03:06:23 PM 1 Genome-wide significant SNPs (some may have
been
> > removed by filtering).
> > 2024/05/14/03:06:23 PM
> > Conversion finished at Tue May 14 15:06:23 2024
> > 2024/05/14/03:06:23 PM Total time elapsed: 28.06s
> > 2024/05/14/03:06:33 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:06:33 PM Munging of Trait 1 complete. SNPs remaining:
> 5099629
> > 2024/05/14/03:06:33 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> >
> > 2024/05/14/03:06:33 PM Warning: The mean chi2 statistic of trait 1 is
> less
> > 1.02 - MTAG estimates may be unstable.
> > 2024/05/14/03:06:51 PM Read in Trait 2 summary statistics (5593073
SNPs)
> > from phen_21_PG_tbn.txt.m.ps ...
> > 2024/05/14/03:06:51 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:06:51 PM Munging Trait 2
> > <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> > 2024/05/14/03:06:51 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:06:51 PM Interpreting column names as follows:
> > 2024/05/14/03:06:51 PM snpid: Variant ID (e.g., rs number)
> > n: Sample size
> > a1: a1, interpreted as ref allele for signed sumstat.
> > pval: p-Value
> > a2: a2, interpreted as non-ref allele for signed sumstat.
> > z: Directional summary statistic as specified by --signed-sumstats.
> >
> > 2024/05/14/03:06:51 PM Reading sumstats from provided DataFrame into
> > memory 10000000 SNPs at a time.
> > 2024/05/14/03:07:00 PM Read 5593073 SNPs from --sumstats file.
> > Removed 0 SNPs with missing values.
> > Removed 0 SNPs with INFO <= None.
> > Removed 0 SNPs with MAF <= 0.01.
> > Removed 0 SNPs with SE <0 or NaN values.
> > Removed 0 SNPs with out-of-bounds p-values.
> > Removed 493444 variants that were not SNPs. Note: strand ambiguous
SNPs
> > were not dropped.
> > 5099629 SNPs remain.
> > 2024/05/14/03:07:03 PM Removed 0 SNPs with duplicated rs numbers
(5099629
> > SNPs remain).
> > 2024/05/14/03:07:04 PM Removed 0 SNPs with N < 815.333333333 (5099629
> SNPs
> > remain).
> > 2024/05/14/03:07:18 PM Median value of SIGNED_SUMSTAT was 0.0122005,
> which
> > seems sensible.
> > 2024/05/14/03:07:18 PM Dropping snps with null values
> > 2024/05/14/03:07:18 PM
> > Metadata:
> > 2024/05/14/03:07:19 PM Mean chi^2 = 0.933
> > 2024/05/14/03:07:19 PM WARNING: mean chi^2 may be too small.
> > 2024/05/14/03:07:19 PM Lambda GC = 0.91
> > 2024/05/14/03:07:19 PM Max chi^2 = 25.301
> > 2024/05/14/03:07:19 PM 0 Genome-wide significant SNPs (some may have
been
> > removed by filtering).
> > 2024/05/14/03:07:19 PM
> > Conversion finished at Tue May 14 15:07:19 2024
> > 2024/05/14/03:07:19 PM Total time elapsed: 28.61s
> > 2024/05/14/03:07:28 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:07:28 PM Munging of Trait 2 complete. SNPs remaining:
> 5099629
> > 2024/05/14/03:07:28 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> >
> > 2024/05/14/03:07:28 PM Warning: The mean chi2 statistic of trait 2 is
> less
> > 1.02 - MTAG estimates may be unstable.
> > 2024/05/14/03:07:47 PM Read in Trait 3 summary statistics (5593073
SNPs)
> > from phen_22_PG_tbn.txt.m.ps ...
> > 2024/05/14/03:07:47 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:07:47 PM Munging Trait 3
> > <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> > 2024/05/14/03:07:47 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:07:47 PM Interpreting column names as follows:
> > 2024/05/14/03:07:47 PM snpid: Variant ID (e.g., rs number)
> > n: Sample size
> > a1: a1, interpreted as ref allele for signed sumstat.
> > pval: p-Value
> > a2: a2, interpreted as non-ref allele for signed sumstat.
> > z: Directional summary statistic as specified by --signed-sumstats.
> >
> > 2024/05/14/03:07:47 PM Reading sumstats from provided DataFrame into
> > memory 10000000 SNPs at a time.
> > 2024/05/14/03:07:58 PM Read 5593073 SNPs from --sumstats file.
> > Removed 0 SNPs with missing values.
> > Removed 0 SNPs with INFO <= None.
> > Removed 0 SNPs with MAF <= 0.01.
> > Removed 0 SNPs with SE <0 or NaN values.
> > Removed 0 SNPs with out-of-bounds p-values.
> > Removed 493444 variants that were not SNPs. Note: strand ambiguous
SNPs
> > were not dropped.
> > 5099629 SNPs remain.
> > 2024/05/14/03:08:02 PM Removed 0 SNPs with duplicated rs numbers
(5099629
> > SNPs remain).
> > 2024/05/14/03:08:03 PM Removed 0 SNPs with N < 815.333333333 (5099629
> SNPs
> > remain).
> > 2024/05/14/03:08:16 PM Median value of SIGNED_SUMSTAT was 0.00952361,
> > which seems sensible.
> > 2024/05/14/03:08:17 PM Dropping snps with null values
> > 2024/05/14/03:08:17 PM
> > Metadata:
> > 2024/05/14/03:08:18 PM Mean chi^2 = 0.951
> > 2024/05/14/03:08:18 PM WARNING: mean chi^2 may be too small.
> > 2024/05/14/03:08:18 PM Lambda GC = 0.934
> > 2024/05/14/03:08:18 PM Max chi^2 = 31.856
> > 2024/05/14/03:08:18 PM 3 Genome-wide significant SNPs (some may have
been
> > removed by filtering).
> > 2024/05/14/03:08:18 PM
> > Conversion finished at Tue May 14 15:08:18 2024
> > 2024/05/14/03:08:18 PM Total time elapsed: 31.07s
> > 2024/05/14/03:08:29 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:08:29 PM Munging of Trait 3 complete. SNPs remaining:
> 5099629
> > 2024/05/14/03:08:29 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> >
> > 2024/05/14/03:08:30 PM Warning: The mean chi2 statistic of trait 3 is
> less
> > 1.02 - MTAG estimates may be unstable.
> > 2024/05/14/03:08:46 PM Dropped 737230 SNPs due to strand ambiguity,
> > 4362399 SNPs remain in intersection after merging trait1
> > 2024/05/14/03:09:03 PM Dropped 0 SNPs due to strand ambiguity, 4362399
> > SNPs remain in intersection after merging trait2
> > 2024/05/14/03:09:22 PM Dropped 0 SNPs due to strand ambiguity, 4362399
> > SNPs remain in intersection after merging trait3
> > 2024/05/14/03:09:22 PM ... Merge of GWAS summary statistics complete.
> > Number of SNPs: 4362399
> > 2024/05/14/03:09:38 PM Using 4362399 SNPs to estimate Omega (0 SNPs
> > excluded due to strand ambiguity)
> > 2024/05/14/03:09:38 PM Estimating sigma..
> > 2024/05/14/03:14:29 PM Checking for positive definiteness ..
> > 2024/05/14/03:14:29 PM Sigma hat:
> > [[1.165 0.97 0.88 ]
> > [0.97 1.177 0.914]
> > [0.88 0.914 1.131]]
> > 2024/05/14/03:14:29 PM Mean chi^2 of SNPs used to estimate Omega is
low
> > for some SNPsMTAG may not perform well in this situation.
> > 2024/05/14/03:14:30 PM Beginning estimation of Omega ...
> > 2024/05/14/03:14:30 PM Using GMM estimator of Omega ..
> > 2024/05/14/03:14:31 PM Checking for positive definiteness ..
> > 2024/05/14/03:14:31 PM matrix is not positive definite, performing
> > adjustment..
> > 2024/05/14/03:14:31 PM Warning: max number of iterations reached in
> > adjustment procedure. Sigma matrix used is still
non-positive-definite.
> > 2024/05/14/03:14:31 PM Completed estimation of Omega ...
> > 2024/05/14/03:14:31 PM Beginning MTAG calculations...
> > 2024/05/14/03:15:19 PM ... Completed MTAG calculations.
> > 2024/05/14/03:15:19 PM Writing Phenotype 1 to file ...
> > 2024/05/14/03:15:58 PM Writing Phenotype 2 to file ...
> > 2024/05/14/03:16:35 PM Writing Phenotype 3 to file ...
> > 2024/05/14/03:17:15 PM
> > Summary of MTAG results:
> > ------------------------
> > Trait # SNPs used N (max) N (mean) GWAS mean chi^2 MTAG mean chi^2
GWAS
> > equiv. (max) N
> > 1 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.807 18.926 -113599
> > 2 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.792 1.771 -4537
> > 3 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.841 1.444 -3409
> >
> > Estimated Omega:
> > [[-1.839e-04 -6.803e-09 -5.303e-09]
> > [-6.803e-09 -2.001e-04 -5.786e-09]
> > [-5.303e-09 -5.786e-09 -1.472e-04]]
> >
> > (Correlation):
> > [[nan nan nan]
> > [nan nan nan]
> > [nan nan nan]]
> >
> > Estimated Sigma:
> > [[1.165 0.97 0.88 ]
> > [0.97 1.177 0.914]
> > [0.88 0.914 1.131]]
> >
> > (Correlation):
> > [[1. 0.828 0.767]
> > [0.828 1. 0.792]
> > [0.767 0.792 1. ]]
> >
> > MTAG weight factors: (average across SNPs)
> > [-0.014 -0.035 0.061]
> >
> > 2024/05/14/03:17:15 PM
> > 2024/05/14/03:17:15 PM MTAG results saved to file.
> > 2024/05/14/03:17:15 PM MTAG complete. Time elapsed:
11.0m:29.370085001s
> >
> > —
> > Reply to this email directly, view it on GitHub
> > <#213 (comment)>,
or
> > unsubscribe
> > <
>
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> >
> > .
> > You are receiving this because you commented.Message ID:
> > ***@***.***>
> >
>
>
> —
> Reply to this email directly, view it on GitHub, or unsubscribe.
> You are receiving this because you authored the thread.Message ID:
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>
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OK，Thank you very much.All the best,Tian在 2024年5月22日，19:07，paturley ***@***.***> 写道：
1000 may be large for maize samples, but it doesn't appear to be large
enough for MTAG, which requires mean chi2 statistics that are greater than
one. Sorry I can't be more helpful.
On Wed, May 22, 2024, 7:02 AM real ***@***.***> wrote:
I have more than 1000 samples which are relatively large for maize
population.Is there other problems？Thank youTian在 2024年5月22日，18:49，paturley
***@***.***> 写道：
Mean chi2 is both a function of heritability and sample size. Your sample
size must be quite small then.
On Wed, May 22, 2024, 5:27 AM real ***@***.***> wrote:
> Hello Patrick
>
>
>
>
> Thanks for your reply. I find that the mean chr^2 of my GWAS results for
> all the traits were less than 1. My phenotype data includes plant
height,
> leaf angle and tassel branch numbers, etc which have higher broad sense
> heritability.Where could this be the problems?
>
>
>
>
> Thank you and all the best,
>
>
>
>
> Tian
>
>
>
>
>
>
>
>
>
>
> At 2024-05-22 04:40:51, "paturley" ***@***.***> wrote:
>
> Ah. So the problem is that your mean chi2 statistics are less than one,
so
> the implicit heritability is negative. I generally recommend that MTAG
not
> be used unless the mean chi2 is at least 1.1 for each trait. Better if
it's
> even higher than that. In your particular case, I think MTAG may not be
the
> right tool.
>
> On Mon, May 20, 2024 at 9:53 PM real ***@***.***> wrote:
>
> > Hello Patrick
> >
> >
> >
> >
> > Thanks for your reply. Yes, I think the results for rep_1 is spurious.
> The
> > Manhattan plots for GWAS and MATG as well as the log file were
attatched.
> >
> >
> >
> >
> > Thank you very much!
> >
> >
> >
> >
> > Best,
> >
> >
> >
> >
> > Tian
> >
> >
> >
> >
> >
> >
> >
> >
> >
> >
> > At 2024-05-21 02:41:50, "paturley" ***@***.***> wrote:
> >
> > Hello Tian,
> >
> > I'm a bit confused by your question. Are you worried that the very
> > significant results for rep_1 is spurious? If you post your log file,
it
> > will help me understand what is going on better.
> >
> > Best,
> > Patrick
> >
> > On Mon, May 20, 2024 at 4:06 AM real ***@***.***> wrote:
> >
> > > Hello,
> > >
> > > I used MTAG to enhance the GWAS ability. I have phenotypic data of
> three
> > > environments of plant hegiht which has low repeatability. We call
the
> > > rep_1,rep_2,rep_3. The GWAS signials were under 1e-5, but the MTAG
> > signials
> > > for rep_1 was under 1e-100, rep_2 and rep_3 were under 1e-5 that
same
> as
> > > the GWAS results. My question are 1) Is MATG suitable for improving
the
> > > detection ability of duplicate data？If so, Is rep_1 an abnormal
result
> > and
> > > how to handle it？
> > >
> > > Thank you very much!
> > >
> > > Tian
> > >
> > > —
> > > Reply to this email directly, view it on GitHub
> > > <#213>, or unsubscribe
> > > <
> >
>
https://github.com/notifications/unsubscribe-auth/AFBUB5LNIGHOATZ7YCQTGRLZDGVHZAVCNFSM6AAAAABH7H4OY2VHI2DSMVQWIX3LMV43ASLTON2WKOZSGMYDKMZYGM4DSMI
> > >
> > > .
> > > You are receiving this because you are subscribed to this
> thread.Message
> > > ID: ***@***.***>
> > >
> >
> >
> > —
> > Reply to this email directly, view it on GitHub, or unsubscribe.
> > You are receiving this because you authored the thread.Message ID:
> > ***@***.***>
> > 2024/05/14/03:05:46 PM
> >
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > <>
> > <> MTAG: Multi-trait Analysis of GWAS
> > <> Version: 1.0.8
> > <> (C) 2017 Omeed Maghzian, Raymond Walters, and Patrick Turley
> > <> Harvard University Department of Economics / Broad Institute of MIT
> and
> > Harvard
> > <> GNU General Public License v3
> >
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > <> Note: It is recommended to run your own QC on the input before
using
> > this program.
> > <> Software-related correspondence: ***@***.***
> > <> All other correspondence: ***@***.***
> >
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> >
> >
> > Calling ./mtag.py \
> > --force \
> > --stream-stdout \
> > --ld-ref-panel /data/ttian/08-GWAS_1223/01_Emmax_1223/5M_Q_K/LDscores/
\
> > --sumstats phen_20_PG_tbn.txt.m.ps,phen_21_PG_tbn.txt.m.ps,
> > phen_22_PG_tbn.txt.m.ps \
> > --out PG/phen_PG_tbn
> >
> > #phen_20_PG_tbn(rep_1),phen_21_PG_tbn(rep_2),phen_22_PG_tbn(rep_3)
> >
> > 2024/05/14/03:05:46 PM Beginning MTAG analysis...
> > 2024/05/14/03:05:46 PM MTAG will use the Z column for analyses.
> > 2024/05/14/03:05:55 PM Read in Trait 1 summary statistics (5593073
SNPs)
> > from phen_20_PG_tbn.txt.m.ps ...
> > 2024/05/14/03:05:55 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:05:55 PM Munging Trait 1
> > <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> > 2024/05/14/03:05:55 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:05:55 PM Interpreting column names as follows:
> > 2024/05/14/03:05:55 PM snpid: Variant ID (e.g., rs number)
> > n: Sample size
> > a1: a1, interpreted as ref allele for signed sumstat.
> > pval: p-Value
> > a2: a2, interpreted as non-ref allele for signed sumstat.
> > z: Directional summary statistic as specified by --signed-sumstats.
> >
> > 2024/05/14/03:05:55 PM Reading sumstats from provided DataFrame into
> > memory 10000000 SNPs at a time.
> > 2024/05/14/03:06:04 PM Read 5593073 SNPs from --sumstats file.
> > Removed 0 SNPs with missing values.
> > Removed 0 SNPs with INFO <= None.
> > Removed 0 SNPs with MAF <= 0.01.
> > Removed 0 SNPs with SE <0 or NaN values.
> > Removed 0 SNPs with out-of-bounds p-values.
> > Removed 493444 variants that were not SNPs. Note: strand ambiguous
SNPs
> > were not dropped.
> > 5099629 SNPs remain.
> > 2024/05/14/03:06:08 PM Removed 0 SNPs with duplicated rs numbers
(5099629
> > SNPs remain).
> > 2024/05/14/03:06:09 PM Removed 0 SNPs with N < 815.333333333 (5099629
> SNPs
> > remain).
> > 2024/05/14/03:06:22 PM Median value of SIGNED_SUMSTAT was 0.000275905,
> > which seems sensible.
> > 2024/05/14/03:06:22 PM Dropping snps with null values
> > 2024/05/14/03:06:22 PM
> > Metadata:
> > 2024/05/14/03:06:23 PM Mean chi^2 = 0.941
> > 2024/05/14/03:06:23 PM WARNING: mean chi^2 may be too small.
> > 2024/05/14/03:06:23 PM Lambda GC = 0.912
> > 2024/05/14/03:06:23 PM Max chi^2 = 30.569
> > 2024/05/14/03:06:23 PM 1 Genome-wide significant SNPs (some may have
been
> > removed by filtering).
> > 2024/05/14/03:06:23 PM
> > Conversion finished at Tue May 14 15:06:23 2024
> > 2024/05/14/03:06:23 PM Total time elapsed: 28.06s
> > 2024/05/14/03:06:33 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:06:33 PM Munging of Trait 1 complete. SNPs remaining:
> 5099629
> > 2024/05/14/03:06:33 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> >
> > 2024/05/14/03:06:33 PM Warning: The mean chi2 statistic of trait 1 is
> less
> > 1.02 - MTAG estimates may be unstable.
> > 2024/05/14/03:06:51 PM Read in Trait 2 summary statistics (5593073
SNPs)
> > from phen_21_PG_tbn.txt.m.ps ...
> > 2024/05/14/03:06:51 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:06:51 PM Munging Trait 2
> > <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> > 2024/05/14/03:06:51 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:06:51 PM Interpreting column names as follows:
> > 2024/05/14/03:06:51 PM snpid: Variant ID (e.g., rs number)
> > n: Sample size
> > a1: a1, interpreted as ref allele for signed sumstat.
> > pval: p-Value
> > a2: a2, interpreted as non-ref allele for signed sumstat.
> > z: Directional summary statistic as specified by --signed-sumstats.
> >
> > 2024/05/14/03:06:51 PM Reading sumstats from provided DataFrame into
> > memory 10000000 SNPs at a time.
> > 2024/05/14/03:07:00 PM Read 5593073 SNPs from --sumstats file.
> > Removed 0 SNPs with missing values.
> > Removed 0 SNPs with INFO <= None.
> > Removed 0 SNPs with MAF <= 0.01.
> > Removed 0 SNPs with SE <0 or NaN values.
> > Removed 0 SNPs with out-of-bounds p-values.
> > Removed 493444 variants that were not SNPs. Note: strand ambiguous
SNPs
> > were not dropped.
> > 5099629 SNPs remain.
> > 2024/05/14/03:07:03 PM Removed 0 SNPs with duplicated rs numbers
(5099629
> > SNPs remain).
> > 2024/05/14/03:07:04 PM Removed 0 SNPs with N < 815.333333333 (5099629
> SNPs
> > remain).
> > 2024/05/14/03:07:18 PM Median value of SIGNED_SUMSTAT was 0.0122005,
> which
> > seems sensible.
> > 2024/05/14/03:07:18 PM Dropping snps with null values
> > 2024/05/14/03:07:18 PM
> > Metadata:
> > 2024/05/14/03:07:19 PM Mean chi^2 = 0.933
> > 2024/05/14/03:07:19 PM WARNING: mean chi^2 may be too small.
> > 2024/05/14/03:07:19 PM Lambda GC = 0.91
> > 2024/05/14/03:07:19 PM Max chi^2 = 25.301
> > 2024/05/14/03:07:19 PM 0 Genome-wide significant SNPs (some may have
been
> > removed by filtering).
> > 2024/05/14/03:07:19 PM
> > Conversion finished at Tue May 14 15:07:19 2024
> > 2024/05/14/03:07:19 PM Total time elapsed: 28.61s
> > 2024/05/14/03:07:28 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:07:28 PM Munging of Trait 2 complete. SNPs remaining:
> 5099629
> > 2024/05/14/03:07:28 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> >
> > 2024/05/14/03:07:28 PM Warning: The mean chi2 statistic of trait 2 is
> less
> > 1.02 - MTAG estimates may be unstable.
> > 2024/05/14/03:07:47 PM Read in Trait 3 summary statistics (5593073
SNPs)
> > from phen_22_PG_tbn.txt.m.ps ...
> > 2024/05/14/03:07:47 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:07:47 PM Munging Trait 3
> > <><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><
> > 2024/05/14/03:07:47 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:07:47 PM Interpreting column names as follows:
> > 2024/05/14/03:07:47 PM snpid: Variant ID (e.g., rs number)
> > n: Sample size
> > a1: a1, interpreted as ref allele for signed sumstat.
> > pval: p-Value
> > a2: a2, interpreted as non-ref allele for signed sumstat.
> > z: Directional summary statistic as specified by --signed-sumstats.
> >
> > 2024/05/14/03:07:47 PM Reading sumstats from provided DataFrame into
> > memory 10000000 SNPs at a time.
> > 2024/05/14/03:07:58 PM Read 5593073 SNPs from --sumstats file.
> > Removed 0 SNPs with missing values.
> > Removed 0 SNPs with INFO <= None.
> > Removed 0 SNPs with MAF <= 0.01.
> > Removed 0 SNPs with SE <0 or NaN values.
> > Removed 0 SNPs with out-of-bounds p-values.
> > Removed 493444 variants that were not SNPs. Note: strand ambiguous
SNPs
> > were not dropped.
> > 5099629 SNPs remain.
> > 2024/05/14/03:08:02 PM Removed 0 SNPs with duplicated rs numbers
(5099629
> > SNPs remain).
> > 2024/05/14/03:08:03 PM Removed 0 SNPs with N < 815.333333333 (5099629
> SNPs
> > remain).
> > 2024/05/14/03:08:16 PM Median value of SIGNED_SUMSTAT was 0.00952361,
> > which seems sensible.
> > 2024/05/14/03:08:17 PM Dropping snps with null values
> > 2024/05/14/03:08:17 PM
> > Metadata:
> > 2024/05/14/03:08:18 PM Mean chi^2 = 0.951
> > 2024/05/14/03:08:18 PM WARNING: mean chi^2 may be too small.
> > 2024/05/14/03:08:18 PM Lambda GC = 0.934
> > 2024/05/14/03:08:18 PM Max chi^2 = 31.856
> > 2024/05/14/03:08:18 PM 3 Genome-wide significant SNPs (some may have
been
> > removed by filtering).
> > 2024/05/14/03:08:18 PM
> > Conversion finished at Tue May 14 15:08:18 2024
> > 2024/05/14/03:08:18 PM Total time elapsed: 31.07s
> > 2024/05/14/03:08:29 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> > 2024/05/14/03:08:29 PM Munging of Trait 3 complete. SNPs remaining:
> 5099629
> > 2024/05/14/03:08:29 PM
> >
>
<><><<>><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><><>
> >
> > 2024/05/14/03:08:30 PM Warning: The mean chi2 statistic of trait 3 is
> less
> > 1.02 - MTAG estimates may be unstable.
> > 2024/05/14/03:08:46 PM Dropped 737230 SNPs due to strand ambiguity,
> > 4362399 SNPs remain in intersection after merging trait1
> > 2024/05/14/03:09:03 PM Dropped 0 SNPs due to strand ambiguity, 4362399
> > SNPs remain in intersection after merging trait2
> > 2024/05/14/03:09:22 PM Dropped 0 SNPs due to strand ambiguity, 4362399
> > SNPs remain in intersection after merging trait3
> > 2024/05/14/03:09:22 PM ... Merge of GWAS summary statistics complete.
> > Number of SNPs: 4362399
> > 2024/05/14/03:09:38 PM Using 4362399 SNPs to estimate Omega (0 SNPs
> > excluded due to strand ambiguity)
> > 2024/05/14/03:09:38 PM Estimating sigma..
> > 2024/05/14/03:14:29 PM Checking for positive definiteness ..
> > 2024/05/14/03:14:29 PM Sigma hat:
> > [[1.165 0.97 0.88 ]
> > [0.97 1.177 0.914]
> > [0.88 0.914 1.131]]
> > 2024/05/14/03:14:29 PM Mean chi^2 of SNPs used to estimate Omega is
low
> > for some SNPsMTAG may not perform well in this situation.
> > 2024/05/14/03:14:30 PM Beginning estimation of Omega ...
> > 2024/05/14/03:14:30 PM Using GMM estimator of Omega ..
> > 2024/05/14/03:14:31 PM Checking for positive definiteness ..
> > 2024/05/14/03:14:31 PM matrix is not positive definite, performing
> > adjustment..
> > 2024/05/14/03:14:31 PM Warning: max number of iterations reached in
> > adjustment procedure. Sigma matrix used is still
non-positive-definite.
> > 2024/05/14/03:14:31 PM Completed estimation of Omega ...
> > 2024/05/14/03:14:31 PM Beginning MTAG calculations...
> > 2024/05/14/03:15:19 PM ... Completed MTAG calculations.
> > 2024/05/14/03:15:19 PM Writing Phenotype 1 to file ...
> > 2024/05/14/03:15:58 PM Writing Phenotype 2 to file ...
> > 2024/05/14/03:16:35 PM Writing Phenotype 3 to file ...
> > 2024/05/14/03:17:15 PM
> > Summary of MTAG results:
> > ------------------------
> > Trait # SNPs used N (max) N (mean) GWAS mean chi^2 MTAG mean chi^2
GWAS
> > equiv. (max) N
> > 1 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.807 18.926 -113599
> > 2 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.792 1.771 -4537
> > 3 ..._PG_tbn.txt.m.ps 4362399 1223 1223 0.841 1.444 -3409
> >
> > Estimated Omega:
> > [[-1.839e-04 -6.803e-09 -5.303e-09]
> > [-6.803e-09 -2.001e-04 -5.786e-09]
> > [-5.303e-09 -5.786e-09 -1.472e-04]]
> >
> > (Correlation):
> > [[nan nan nan]
> > [nan nan nan]
> > [nan nan nan]]
> >
> > Estimated Sigma:
> > [[1.165 0.97 0.88 ]
> > [0.97 1.177 0.914]
> > [0.88 0.914 1.131]]
> >
> > (Correlation):
> > [[1. 0.828 0.767]
> > [0.828 1. 0.792]
> > [0.767 0.792 1. ]]
> >
> > MTAG weight factors: (average across SNPs)
> > [-0.014 -0.035 0.061]
> >
> > 2024/05/14/03:17:15 PM
> > 2024/05/14/03:17:15 PM MTAG results saved to file.
> > 2024/05/14/03:17:15 PM MTAG complete. Time elapsed:
11.0m:29.370085001s
> >
> > —
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Hello,
I used MTAG to enhance the GWAS ability. I have phenotypic data of three environments of plant hegiht which has low repeatability. We call the rep_1,rep_2,rep_3. The GWAS signials were under 1e-5, but the MTAG signials for rep_1 was under 1e-100, rep_2 and rep_3 were under 1e-5 that same as the GWAS results. My question are 1) Is MATG suitable for improving the detection ability of duplicate data？If so, Is rep_1 an abnormal result and how to handle it？
Thank you very much!
Tian
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