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"gwas_harmonisation_command": "--json /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-180/ukb-a-180_data.json --ref /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/QC/genomes/b37/human_g1k_v37.fasta; 1.1.1",
"file_date": "2020-02-16T02:07:15.800719",
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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-180/ukb-a-180.vcf.gz -O z /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-180/ukb-a-180_data.vcf.gz; Date=Sun Feb 16 02:24:39 2020",
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"bcftools_viewCommand": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-a-180/ukb-a-180.vcf.gz; Date=Sun May 10 06:12:12 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-180/ukb-a-180.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-180/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 02:50:21 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-180/ukb-a-180.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: 0.0038 (0.0014)
Lambda GC: 1.0156
Mean Chi^2: 1.0319
Intercept: 1.0068 (0.0062)
Ratio: 0.2117 (0.1948)
Analysis finished at Sun Feb 16 02:52:09 2020
Total time elapsed: 1.0m:47.41s
{
"af_correlation": 0.9533,
"inflation_factor": 1.0167,
"mean_EFFECT": 3.3644e-06,
"n": 337159,
"n_snps": 10877936,
"n_clumped_hits": 2,
"n_p_sig": 67,
"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": 335661.2287,
"ratio_se_n": 0.9978,
"mean_diff": 0,
"ratio_diff": 29.1939,
"sd_y_est1": 0.0799,
"sd_y_est2": 0.0797,
"r2_sum1": 1.6261e-06,
"r2_sum2": 0.0003,
"r2_sum3": 0.0003,
"r2_sum4": 0.0003,
"ldsc_nsnp_merge_refpanel_ld": 1281483,
"ldsc_nsnp_merge_regression_ld": 1281483,
"ldsc_observed_scale_h2_beta": 0.0038,
"ldsc_observed_scale_h2_se": 0.0014,
"ldsc_intercept_beta": 1.0068,
"ldsc_intercept_se": 0.0062,
"ldsc_lambda_gc": 1.0156,
"ldsc_mean_chisq": 1.0319,
"ldsc_ratio": 0.2132
}
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 | 3.400000e-06 | 1.156300e-03 | -1.33834e-02 | -3.227000e-04 | -6.200000e-06 | 3.040000e-04 | 1.860030e-02 | ▁▂▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 8.379000e-04 | 7.936000e-04 | 1.92200e-04 | 2.374000e-04 | 4.560000e-04 | 1.218500e-03 | 4.367800e-03 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.973844e-01 | 2.894117e-01 | 0.00000e+00 | 2.460560e-01 | 4.964437e-01 | 7.482298e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.973840e-01 | 2.894120e-01 | 0.00000e+00 | 2.460552e-01 | 4.964433e-01 | 7.482295e-01 | 9.999999e-01 | ▇▇▇▇▇ |
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 | -0.0000556 | 0.0003209 | 0.8624539 | 0.8624538 | 0.1169260 | 0.1417730 | 337159 |
1 | 717587 | rs144155419 | G | A | 0.0011459 | 0.0008619 | 0.1836801 | 0.1836790 | 0.0143862 | 0.0045926 | 337159 |
1 | 730087 | rs148120343 | T | C | -0.0000383 | 0.0004471 | 0.9317451 | 0.9317447 | 0.0554733 | 0.0127796 | 337159 |
1 | 731718 | rs142557973 | T | C | 0.0000963 | 0.0003044 | 0.7517891 | 0.7517889 | 0.1216580 | 0.1543530 | 337159 |
1 | 734349 | rs141242758 | T | C | 0.0001027 | 0.0003046 | 0.7360427 | 0.7360430 | 0.1215130 | 0.1525560 | 337159 |
1 | 740284 | rs61770167 | C | T | -0.0014614 | 0.0013865 | 0.2918798 | 0.2918803 | 0.0058556 | 0.0023962 | 337159 |
1 | 742813 | rs112573343 | C | T | 0.0002971 | 0.0026165 | 0.9095919 | 0.9095918 | 0.0015525 | 0.1030350 | 337159 |
1 | 753405 | rs3115860 | C | A | -0.0001274 | 0.0002894 | 0.6597251 | 0.6597248 | 0.8706760 | 0.7517970 | 337159 |
1 | 753541 | rs2073813 | G | A | 0.0001335 | 0.0002901 | 0.6454075 | 0.6454073 | 0.1288330 | 0.3019170 | 337159 |
1 | 754182 | rs3131969 | A | G | -0.0001188 | 0.0002891 | 0.6809826 | 0.6809826 | 0.8703180 | 0.6785140 | 337159 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219387 | rs9616832 | T | C | -0.0003193 | 0.0003727 | 0.3916688 | 0.3916682 | 0.0729806 | 0.0654952 | 337159 |
22 | 51219704 | rs147475742 | G | A | -0.0000026 | 0.0004996 | 0.9957840 | 0.9957840 | 0.0418225 | 0.0473243 | 337159 |
22 | 51219766 | rs182321900 | C | T | 0.0018912 | 0.0025686 | 0.4615598 | 0.4615593 | 0.0014546 | NA | 337159 |
22 | 51220088 | rs566371895 | G | A | 0.0021391 | 0.0016801 | 0.2029528 | 0.2029514 | 0.0039843 | 0.0003994 | 337159 |
22 | 51220146 | rs868950473 | C | T | 0.0015273 | 0.0025302 | 0.5460998 | 0.5460998 | 0.0015139 | NA | 337159 |
22 | 51221731 | rs115055839 | T | C | -0.0003389 | 0.0003730 | 0.3635423 | 0.3635419 | 0.0728101 | 0.0625000 | 337159 |
22 | 51223637 | rs375798137 | G | A | 0.0013525 | 0.0004393 | 0.0020799 | 0.0020797 | 0.0540289 | 0.0788738 | 337159 |
22 | 51226692 | rs150189434 | G | A | 0.0021629 | 0.0026270 | 0.4103345 | 0.4103317 | 0.0013983 | 0.0155751 | 337159 |
22 | 51229805 | rs9616985 | T | C | -0.0003356 | 0.0003744 | 0.3699398 | 0.3699392 | 0.0727671 | 0.0730831 | 337159 |
22 | 51237063 | rs3896457 | T | C | 0.0002243 | 0.0002278 | 0.3249399 | 0.3249381 | 0.2968410 | 0.2050720 | 337159 |
1 693731 rs12238997 A G . PASS AF=0.116926 ES:SE:LP:AF:SS:ID -5.55917e-05:0.000320873:0.0642641:0.116926:337159:rs12238997
1 717587 rs144155419 G A . PASS AF=0.0143862 ES:SE:LP:AF:SS:ID 0.0011459:0.000861895:0.735938:0.0143862:337159:rs144155419
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1 731718 rs58276399 T C . PASS AF=0.121658 ES:SE:LP:AF:SS:ID 9.62805e-05:0.000304414:0.123904:0.121658:337159:rs58276399
1 734349 rs141242758 T C . PASS AF=0.121513 ES:SE:LP:AF:SS:ID 0.000102676:0.000304588:0.133097:0.121513:337159:rs141242758
1 740284 rs61770167 C T . PASS AF=0.00585559 ES:SE:LP:AF:SS:ID -0.0014614:0.00138652:0.534796:0.00585559:337159:rs61770167
1 742813 rs112573343 C T . PASS AF=0.0015525 ES:SE:LP:AF:SS:ID 0.000297117:0.00261654:0.0411534:0.0015525:337159:rs112573343
1 753405 rs3115860 C A . PASS AF=0.870676 ES:SE:LP:AF:SS:ID -0.000127416:0.000289389:0.180637:0.870676:337159:rs3115860
1 753541 rs2073813 G A . PASS AF=0.128833 ES:SE:LP:AF:SS:ID 0.000133496:0.000290113:0.190166:0.128833:337159:rs2073813
1 754182 rs3131969 A G . PASS AF=0.870318 ES:SE:LP:AF:SS:ID -0.000118849:0.000289084:0.166864:0.870318:337159:rs3131969
1 754192 rs3131968 A G . PASS AF=0.870409 ES:SE:LP:AF:SS:ID -0.000126135:0.00028922:0.17865:0.870409:337159:rs3131968
1 754334 rs3131967 T C . PASS AF=0.870037 ES:SE:LP:AF:SS:ID -0.000118464:0.000289072:0.166249:0.870037:337159:rs3131967
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1 754458 rs142682604 G T . PASS AF=0.00464711 ES:SE:LP:AF:SS:ID 0.00204081:0.0014789:0.775716:0.00464711:337159:rs142682604
1 755435 rs184270342 T G . PASS AF=0.00590897 ES:SE:LP:AF:SS:ID 0.000600524:0.0014402:0.169604:0.00590897:337159:rs184270342
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1 768448 rs12562034 G A . PASS AF=0.105257 ES:SE:LP:AF:SS:ID -0.000100391:0.000314927:0.124998:0.105257:337159:rs12562034
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1 769224 rs141644775 G A . PASS AF=0.00143239 ES:SE:LP:AF:SS:ID -0.000350109:0.00272188:0.046892:0.00143239:337159:rs141644775
1 770181 rs146076599 A G . PASS AF=0.00907328 ES:SE:LP:AF:SS:ID 0.000823204:0.00111011:0.338795:0.00907328:337159:rs146076599
1 770377 rs112563271 A T . PASS AF=0.00692321 ES:SE:LP:AF:SS:ID -0.00178032:0.00117506:0.886893:0.00692321:337159:rs112563271
1 771823 rs2977605 T C . PASS AF=0.869934 ES:SE:LP:AF:SS:ID -0.000112136:0.000288397:0.156515:0.869934:337159:rs2977605
1 771967 rs59066358 G A . PASS AF=0.128709 ES:SE:LP:AF:SS:ID 0.000116151:0.00028955:0.162213:0.128709:337159:rs59066358
1 772755 rs2905039 A C . PASS AF=0.870112 ES:SE:LP:AF:SS:ID -0.000112935:0.00028841:0.157783:0.870112:337159:rs2905039
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1 777122 rs2980319 A T . PASS AF=0.871122 ES:SE:LP:AF:SS:ID -9.45838e-05:0.000288901:0.128794:0.871122:337159:rs2980319
1 777232 rs112618790 C T . PASS AF=0.0961319 ES:SE:LP:AF:SS:ID -3.92307e-05:0.00033355:0.0426935:0.0961319:337159:rs112618790
1 778745 rs1055606 A G . PASS AF=0.127871 ES:SE:LP:AF:SS:ID 0.000106221:0.000289849:0.146293:0.127871:337159:rs1055606
1 779322 rs4040617 A G . PASS AF=0.127984 ES:SE:LP:AF:SS:ID 0.000100354:0.000289458:0.137379:0.127984:337159:rs4040617
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1 781367 rs149821290 A C . PASS AF=0.00989772 ES:SE:LP:AF:SS:ID -0.000697384:0.00102652:0.303725:0.00989772:337159:rs149821290
1 781845 rs61768199 A G . PASS AF=0.1044 ES:SE:LP:AF:SS:ID -9.53945e-05:0.000324341:0.114261:0.1044:337159:rs61768199
1 782721 rs185280546 G A . PASS AF=0.0143713 ES:SE:LP:AF:SS:ID 4.53863e-05:0.000877901:0.018286:0.0143713:337159:rs185280546
1 782981 rs6594026 C T . PASS AF=0.128338 ES:SE:LP:AF:SS:ID 0.000142752:0.000289616:0.206152:0.128338:337159:rs6594026
1 783193 rs145767270 G C . PASS AF=0.0143639 ES:SE:LP:AF:SS:ID 6.18816e-05:0.000881624:0.0250087:0.0143639:337159:rs145767270
1 783194 rs138555831 G T . PASS AF=0.0143713 ES:SE:LP:AF:SS:ID 5.658e-05:0.000881517:0.0228148:0.0143713:337159:rs138555831
1 783711 rs184266993 G A . PASS AF=0.00541372 ES:SE:LP:AF:SS:ID -0.000409971:0.0014094:0.112866:0.00541372:337159:rs184266993
1 785050 rs2905062 G A . PASS AF=0.87014 ES:SE:LP:AF:SS:ID -0.000124669:0.000288471:0.176776:0.87014:337159:rs2905062
1 785989 rs2980300 T C . PASS AF=0.87009 ES:SE:LP:AF:SS:ID -0.000126743:0.000288654:0.18006:0.87009:337159:rs2980300