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"gwas_harmonisation_command": "--json /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-109/ukb-a-109_data.json --ref /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/QC/genomes/b37/human_g1k_v37.fasta; 1.1.1",
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"bcftools_annotateCommand": "annotate -a /mnt/storage/home/gh13047/mr-eve/vcf-reference-datasets/dbsnp/dbsnp.v153.b37.vcf.gz -c ID -o /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-109/ukb-a-109.vcf.gz -O z /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-109/ukb-a-109_data.vcf.gz; Date=Sun Feb 16 01:34:05 2020",
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"bcftools_viewCommand": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-a-109/ukb-a-109.vcf.gz; Date=Sun May 10 01:16:40 2020"
}
*********************************************************************
* LD Score Regression (LDSC)
* Version 1.0.1
* (C) 2014-2019 Brendan Bulik-Sullivan and Hilary Finucane
* Broad Institute of MIT and Harvard / MIT Department of Mathematics
* GNU General Public License v3
*********************************************************************
Call:
./ldsc.py \
--h2 /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-109/ukb-a-109.vcf.gz \
--ref-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-109/ldsc.txt \
--w-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/
Beginning analysis at Sun Feb 16 01:56:53 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-109/ukb-a-109.vcf.gz ...
Read summary statistics for 10877936 SNPs.
Reading reference panel LD Score from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/[1-22] ...
Read reference panel LD Scores for 1290028 SNPs.
Removing partitioned LD Scores with zero variance.
Reading regression weight LD Score from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/[1-22] ...
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1281483 SNPs remain.
After merging with regression SNP LD, 1281483 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.008 (0.0013)
Lambda GC: 1.0835
Mean Chi^2: 1.0844
Intercept: 1.0321 (0.006)
Ratio: 0.3801 (0.0714)
Analysis finished at Sun Feb 16 01:58:38 2020
Total time elapsed: 1.0m:44.84s
{
"af_correlation": 0.9533,
"inflation_factor": 1.0588,
"mean_EFFECT": 5.7102e-06,
"n": 337159,
"n_snps": 10877936,
"n_clumped_hits": 2,
"n_p_sig": 3,
"n_mono": 0,
"n_ns": 0,
"n_mac": 0,
"is_snpid_unique": true,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 0,
"n_miss_AF_reference": 356865,
"n_est": 335660.7565,
"ratio_se_n": 0.9978,
"mean_diff": 0,
"ratio_diff": 36.4592,
"sd_y_est1": 0.1519,
"sd_y_est2": 0.1516,
"r2_sum1": 4.3343e-06,
"r2_sum2": 0.0002,
"r2_sum3": 0.0002,
"r2_sum4": 0.0002,
"ldsc_nsnp_merge_refpanel_ld": 1281483,
"ldsc_nsnp_merge_regression_ld": 1281483,
"ldsc_observed_scale_h2_beta": 0.008,
"ldsc_observed_scale_h2_se": 0.0013,
"ldsc_intercept_beta": 1.0321,
"ldsc_intercept_se": 0.006,
"ldsc_lambda_gc": 1.0835,
"ldsc_mean_chisq": 1.0844,
"ldsc_ratio": 0.3803
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | FALSE |
n | FALSE |
is_snpid_non_unique | FALSE |
mean_EFFECT_nonfinite | FALSE |
mean_EFFECT_05 | FALSE |
mean_EFFECT_01 | FALSE |
mean_chisq | FALSE |
n_p_sig | FALSE |
miss_EFFECT | FALSE |
miss_SE | FALSE |
miss_PVAL | FALSE |
ldsc_ratio | FALSE |
ldsc_intercept_beta | FALSE |
n_clumped_hits | FALSE |
r2_sum1 | FALSE |
r2_sum2 | FALSE |
r2_sum3 | FALSE |
r2_sum4 | FALSE |
General metrics
af_correlation
: Correlation coefficient between AF
and AF_reference
.inflation_factor
(lambda
): Genomic inflation factor.mean_EFFECT
: Mean of EFFECT
size.n
: Maximum value of reported sample size across all SNPs, \(n\).n_clumped_hits
: Number of clumped hits.n_snps
: Number of SNPsn_p_sig
: Number of SNPs with pvalue below 5e-8
.n_mono
: Number of monomorphic (MAF == 1
or MAF == 0
) SNPs.n_ns
: Number of SNPs with nonsense values:
A, C, G or T
.< 0
or > 1
.<= 0
or = Infinity
).< 0
or > 1
.n_mac
: Number of cases where MAC
(\(2 \times N \times MAF\)) is less than 6
.is_snpid_unique
: true
if the combination of ID
REF
ALT
is unique and therefore no duplication in snpid.n_miss_<*>
: Number of NA
observations for <*>
column.se_n metrics
n_est
: Estimated sample size value, \(\widehat{n}\).ratio_se_n
: \(\texttt{ratio_se_n} = \frac{\sqrt{\widehat{n}}}{\sqrt{n}}\). We expect ratio_se_n
to be 1. When it is not 1, it implies that the trait did not have a variance of 1, the reported sample size is wrong, or that the SNP-level effective sample sizes differ markedly from the reported sample size.mean_diff
: \(\texttt{mean_diff} = \sum_{j} \frac{\widehat{\beta_j^{std}} - \beta_j}{\texttt{n_snps}}\), mean difference between the standardised beta, predicted from P-values, and the observed beta. The difference should be very close to zero if trait has a variance of 1.
ratio_diff
: \(\texttt{ratio_diff} = |\frac{\texttt{mean_diff}}{\texttt{mean_diff2}}|\), absolute ratio between the mean of diff
and the mean of diff2
(expected difference between the standardised beta predicted from P-values, and the standardised beta derived from the observed beta divided by the predicted SD; NOT reported). The ratio should be close to 1. If different from 1, then implies that the betas are not in a standard deviation scale.
sd_y_est1
: The standard deviation for the trait inferred from the reported sample size, median standard errors for the SNP-trait assocations and SNP variances.
sd_y_est2
: The standard deviation for the trait inferred from the reported sample size, Z statistics for the SNP-trait effects (beta/se) and allele frequency.
r2 metrics
Sum of variance explained, calculated from the clumped top hits sample.
r2_sum<*>
: r2
statistics under various assumptions
1
: \(r^2 = \sum_j{\frac{2 \times \beta_j^2 \times {MAF}_j \times (1 - {MAF}_j)}{\texttt{var1}}}\), \(\texttt{var1} = 1\).2
: \(r^2 = \sum_j{\frac{2 \times \beta_j^2 \times {MAF}_j \times (1 - {MAF}_j)}{\texttt{var2}}}\), \(\texttt{var2} = {\widehat{\texttt{sd1}}_{y}}^2\),3
: \(r^2 = \sum_j{\frac{2 \times \beta_j^2 \times {MAF}_j \times (1 - {MAF}_j)}{\texttt{var3}}}\), \(\texttt{var3} = {\widehat{\texttt{sd2}}_{y}}^2\),4
: \(r^2 = \sum_j{\frac{F_j}{F_j + n - 2}}\), \(F = \frac{\beta_j^2}{{se}_j^2}\).LDSC metrics
Metrics from LD regression
ldsc_nsnp_merge_refpanel_ld
: Number of remaining SNPs after merging with reference panel LD.ldsc_nsnp_merge_regression_ld
: Number of remaining SNPs after merging with regression SNP LD.ldsc_observed_scale_h2_{beta,se}
Coefficient value and SE for total observed scale h2.ldsc_intercept_{beta,se}
: Coefficient value and SE for intercept. Intercept is expected to be 1.ldsc_lambda_gc
: Lambda GC statistics.ldsc_mean_chisq
: Mean \(\chi^2\) statistics.ldsc_ratio
: \(\frac{\texttt{ldsc_intercept_beta} - 1}{\texttt{ldsc_mean_chisq} - 1}\), the proportion of the inflation in the mean \(\chi^2\) that the LD Score regression intercepts ascribes to causes other than polygenic heritability. The value of ratio should be close to zero, though in practice values of 0.1-0.2 are not uncommon, probably due to sample/reference LD Score mismatch or model misspecification (e.g., low LD variants have slightly higher \(h^2\) per SNP).Flags
When a metric needs attention, the flag should return TRUE.
af_correlation
: abs(af_correlation)
< 0.7.inflation_factor
: inflation_factor
> 1.2.n
: n
(max reported sample size) < 10000.is_snpid_non_unique
: NOT is_snpid_unique
.mean_EFFECT_nonfinite
: mean(EFFECT)
is NA
, NaN
, or Inf
.mean_EFFECT_05
: abs(mean(EFFECT))
> 0.5.mean_EFFECT_01
: abs(mean(EFFECT))
> 0.1.mean_chisq
: ldsc_mean_chisq
> 1.3 or ldsc_mean_chisq
< 0.7.n_p_sig
: n_p_sig
> 1000.miss_<*>
: n_miss_<*>
/ n_snps
> 0.01.ldsc_ratio
: ldsc_ratio
> 0.5ldsc_intercept_beta
: ldsc_intercept_beta
> 1.5n_clumped_hits
: n_clumped_hits
> 1000r2_sum<*>
: r2_sum<*>
> 0.5Plots
skim_type | skim_variable | n_missing | complete_rate | character.min | character.max | character.empty | character.n_unique | character.whitespace | numeric.mean | numeric.sd | numeric.p0 | numeric.p25 | numeric.p50 | numeric.p75 | numeric.p100 | numeric.hist |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
character | ID | 0 | 1.0000000 | 3 | 58 | 0 | 10877936 | 0 | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA |
numeric | CHROM | 0 | 1.0000000 | NA | NA | NA | NA | NA | 8.598638e+00 | 5.745666e+00 | 1.00000e+00 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▃▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.911383e+07 | 5.624931e+07 | 8.28000e+02 | 3.287294e+07 | 6.988889e+07 | 1.148258e+08 | 2.492251e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | 5.700000e-06 | 2.213100e-03 | -2.35408e-02 | -6.177000e-04 | -8.000000e-06 | 5.979000e-04 | 2.903550e-02 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 1.593700e-03 | 1.509400e-03 | 3.65600e-04 | 4.516000e-04 | 8.673000e-04 | 2.317600e-03 | 8.307700e-03 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.908976e-01 | 2.905038e-01 | 0.00000e+00 | 2.374390e-01 | 4.876520e-01 | 7.416568e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.908972e-01 | 2.905041e-01 | 0.00000e+00 | 2.374382e-01 | 4.876515e-01 | 7.416559e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | 1.820865e-01 | 2.503832e-01 | 1.00090e-03 | 6.878700e-03 | 5.191440e-02 | 2.739880e-01 | 9.989990e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 356865 | 0.9671937 | NA | NA | NA | NA | NA | 1.877709e-01 | 2.439191e-01 | 0.00000e+00 | 5.191700e-03 | 7.468050e-02 | 2.873400e-01 | 1.000000e+00 | ▇▂▁▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | 3.371590e+05 | 0.000000e+00 | 3.37159e+05 | 3.371590e+05 | 3.371590e+05 | 3.371590e+05 | 3.371590e+05 | ▁▁▇▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 693731 | rs12238997 | A | G | 0.0004472 | 0.0006103 | 0.4637405 | 0.4637400 | 0.1169260 | 0.1417730 | 337159 |
1 | 717587 | rs144155419 | G | A | -0.0002289 | 0.0016394 | 0.8889329 | 0.8889330 | 0.0143862 | 0.0045926 | 337159 |
1 | 730087 | rs148120343 | T | C | 0.0003304 | 0.0008504 | 0.6976201 | 0.6976195 | 0.0554733 | 0.0127796 | 337159 |
1 | 731718 | rs142557973 | T | C | 0.0005276 | 0.0005790 | 0.3621596 | 0.3621602 | 0.1216580 | 0.1543530 | 337159 |
1 | 734349 | rs141242758 | T | C | 0.0005575 | 0.0005793 | 0.3358853 | 0.3358842 | 0.1215130 | 0.1525560 | 337159 |
1 | 740284 | rs61770167 | C | T | -0.0008063 | 0.0026372 | 0.7597977 | 0.7597967 | 0.0058556 | 0.0023962 | 337159 |
1 | 742813 | rs112573343 | C | T | -0.0017929 | 0.0049768 | 0.7186543 | 0.7186548 | 0.0015525 | 0.1030350 | 337159 |
1 | 753405 | rs3115860 | C | A | -0.0004659 | 0.0005504 | 0.3973443 | 0.3973421 | 0.8706760 | 0.7517970 | 337159 |
1 | 753541 | rs2073813 | G | A | 0.0004130 | 0.0005518 | 0.4542218 | 0.4542221 | 0.1288330 | 0.3019170 | 337159 |
1 | 754182 | rs3131969 | A | G | -0.0005095 | 0.0005498 | 0.3541498 | 0.3541496 | 0.8703180 | 0.6785140 | 337159 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219387 | rs9616832 | T | C | 0.0006988 | 0.0007089 | 0.3242881 | 0.3242869 | 0.0729806 | 0.0654952 | 337159 |
22 | 51219704 | rs147475742 | G | A | 0.0004273 | 0.0009503 | 0.6529847 | 0.6529842 | 0.0418225 | 0.0473243 | 337159 |
22 | 51219766 | rs182321900 | C | T | -0.0039938 | 0.0048857 | 0.4136747 | 0.4136738 | 0.0014546 | NA | 337159 |
22 | 51220088 | rs566371895 | G | A | 0.0003380 | 0.0031956 | 0.9157569 | 0.9157568 | 0.0039843 | 0.0003994 | 337159 |
22 | 51220146 | rs868950473 | C | T | -0.0053985 | 0.0048125 | 0.2619588 | 0.2619583 | 0.0015139 | NA | 337159 |
22 | 51221731 | rs115055839 | T | C | 0.0007018 | 0.0007094 | 0.3224668 | 0.3224666 | 0.0728101 | 0.0625000 | 337159 |
22 | 51223637 | rs375798137 | G | A | -0.0001721 | 0.0008356 | 0.8367860 | 0.8367855 | 0.0540289 | 0.0788738 | 337159 |
22 | 51226692 | rs150189434 | G | A | -0.0049784 | 0.0049967 | 0.3190913 | 0.3190900 | 0.0013983 | 0.0155751 | 337159 |
22 | 51229805 | rs9616985 | T | C | 0.0006924 | 0.0007120 | 0.3308423 | 0.3308410 | 0.0727671 | 0.0730831 | 337159 |
22 | 51237063 | rs3896457 | T | C | -0.0004217 | 0.0004333 | 0.3305270 | 0.3305268 | 0.2968410 | 0.2050720 | 337159 |
1 693731 rs12238997 A G . PASS AF=0.116926 ES:SE:LP:AF:SS:ID 0.000447177:0.000610312:0.333725:0.116926:337159:rs12238997
1 717587 rs144155419 G A . PASS AF=0.0143862 ES:SE:LP:AF:SS:ID -0.000228944:0.00163936:0.051131:0.0143862:337159:rs144155419
1 730087 rs148120343 T C . PASS AF=0.0554733 ES:SE:LP:AF:SS:ID 0.00033043:0.000850449:0.156381:0.0554733:337159:rs148120343
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1 734349 rs141242758 T C . PASS AF=0.121513 ES:SE:LP:AF:SS:ID 0.000557512:0.000579336:0.473809:0.121513:337159:rs141242758
1 740284 rs61770167 C T . PASS AF=0.00585559 ES:SE:LP:AF:SS:ID -0.000806321:0.00263721:0.119302:0.00585559:337159:rs61770167
1 742813 rs112573343 C T . PASS AF=0.0015525 ES:SE:LP:AF:SS:ID -0.00179291:0.00497675:0.14348:0.0015525:337159:rs112573343
1 753405 rs3115860 C A . PASS AF=0.870676 ES:SE:LP:AF:SS:ID -0.00046587:0.000550428:0.400833:0.870676:337159:rs3115860
1 753541 rs2073813 G A . PASS AF=0.128833 ES:SE:LP:AF:SS:ID 0.000412968:0.000551805:0.342732:0.128833:337159:rs2073813
1 754182 rs3131969 A G . PASS AF=0.870318 ES:SE:LP:AF:SS:ID -0.000509472:0.000549847:0.450813:0.870318:337159:rs3131969
1 754192 rs3131968 A G . PASS AF=0.870409 ES:SE:LP:AF:SS:ID -0.0005061:0.000550107:0.446636:0.870409:337159:rs3131968
1 754334 rs3131967 T C . PASS AF=0.870037 ES:SE:LP:AF:SS:ID -0.000523365:0.000549825:0.467042:0.870037:337159:rs3131967
1 754433 rs150578204 G A . PASS AF=0.00465304 ES:SE:LP:AF:SS:ID -6.16608e-05:0.00280529:0.00768335:0.00465304:337159:rs150578204
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1 755435 rs184270342 T G . PASS AF=0.00590897 ES:SE:LP:AF:SS:ID 0.000706077:0.00273931:0.098763:0.00590897:337159:rs184270342
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1 758626 rs3131954 C T . PASS AF=0.870396 ES:SE:LP:AF:SS:ID -0.000463755:0.00054947:0.399389:0.870396:337159:rs3131954
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1 766007 rs61768174 A C . PASS AF=0.106958 ES:SE:LP:AF:SS:ID 0.000428347:0.000608896:0.317173:0.106958:337159:rs61768174
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1 770377 rs112563271 A T . PASS AF=0.00692321 ES:SE:LP:AF:SS:ID -0.00234591:0.00223501:0.531812:0.00692321:337159:rs112563271
1 771823 rs2977605 T C . PASS AF=0.869934 ES:SE:LP:AF:SS:ID -0.000447367:0.000548541:0.38221:0.869934:337159:rs2977605
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1 772755 rs2905039 A C . PASS AF=0.870112 ES:SE:LP:AF:SS:ID -0.000453142:0.000548565:0.388514:0.870112:337159:rs2905039
1 774736 rs28830877 A C . PASS AF=0.998797 ES:SE:LP:AF:SS:ID -0.0076159:0.00569877:0.741324:0.998797:337159:rs28830877
1 776556 rs151160018 C T . PASS AF=0.00851871 ES:SE:LP:AF:SS:ID 0.00250538:0.00205862:0.650534:0.00851871:337159:rs151160018
1 777122 rs2980319 A T . PASS AF=0.871122 ES:SE:LP:AF:SS:ID -0.000486418:0.000549499:0.424757:0.871122:337159:rs2980319
1 777232 rs112618790 C T . PASS AF=0.0961319 ES:SE:LP:AF:SS:ID -0.000377332:0.000634424:0.258059:0.0961319:337159:rs112618790
1 778745 rs1055606 A G . PASS AF=0.127871 ES:SE:LP:AF:SS:ID 0.000407494:0.000551303:0.337413:0.127871:337159:rs1055606
1 779322 rs4040617 A G . PASS AF=0.127984 ES:SE:LP:AF:SS:ID 0.000389982:0.000550559:0.319904:0.127984:337159:rs4040617
1 780785 rs2977612 T A . PASS AF=0.870455 ES:SE:LP:AF:SS:ID -0.000436983:0.000548598:0.370879:0.870455:337159:rs2977612
1 781367 rs149821290 A C . PASS AF=0.00989772 ES:SE:LP:AF:SS:ID -0.00505884:0.00195247:2.01908:0.00989772:337159:rs149821290
1 781845 rs61768199 A G . PASS AF=0.1044 ES:SE:LP:AF:SS:ID 0.000566498:0.000616907:0.445548:0.1044:337159:rs61768199
1 782721 rs185280546 G A . PASS AF=0.0143713 ES:SE:LP:AF:SS:ID -0.000350406:0.0016698:0.0789454:0.0143713:337159:rs185280546
1 782981 rs6594026 C T . PASS AF=0.128338 ES:SE:LP:AF:SS:ID 0.000397053:0.00055086:0.326942:0.128338:337159:rs6594026
1 783193 rs145767270 G C . PASS AF=0.0143639 ES:SE:LP:AF:SS:ID -0.000523655:0.00167688:0.122152:0.0143639:337159:rs145767270
1 783194 rs138555831 G T . PASS AF=0.0143713 ES:SE:LP:AF:SS:ID -0.000535141:0.00167668:0.12517:0.0143713:337159:rs138555831
1 783711 rs184266993 G A . PASS AF=0.00541372 ES:SE:LP:AF:SS:ID 0.000567589:0.00268074:0.0797102:0.00541372:337159:rs184266993
1 785050 rs2905062 G A . PASS AF=0.87014 ES:SE:LP:AF:SS:ID -0.000463745:0.000548681:0.400117:0.87014:337159:rs2905062
1 785989 rs2980300 T C . PASS AF=0.87009 ES:SE:LP:AF:SS:ID -0.00045398:0.000549029:0.389013:0.87009:337159:rs2980300