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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/e0844a94-2add-455f-b114-888a1e457605/call-vcf/inputs/-674580007/upload.txt.gz --id ieu-b-7 --json /data/cromwell-executions/qc/e0844a94-2add-455f-b114-888a1e457605/call-vcf/inputs/-674580007/ieu-b-7_data.json --ref /data/cromwell-executions/qc/e0844a94-2add-455f-b114-888a1e457605/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/e0844a94-2add-455f-b114-888a1e457605/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-7/ieu-b-7.vcf.gz --rm_chr_prefix --cohort_cases 33674 --cohort_controls 449056; 1.2.1",
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}
*********************************************************************
* 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 /data/cromwell-executions/qc/e0844a94-2add-455f-b114-888a1e457605/call-ldsc/inputs/-674580007/ieu-b-7.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-7/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Tue Jun 23 15:55:19 2020
Reading summary statistics from /data/cromwell-executions/qc/e0844a94-2add-455f-b114-888a1e457605/call-ldsc/inputs/-674580007/ieu-b-7.vcf.gz ...
Read summary statistics for 17891839 SNPs.
Dropped 488494 SNPs with duplicated rs numbers.
Reading reference panel LD Score from /data/ref/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 /data/ref/eur_w_ld_chr/[1-22] ...
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1217474 SNPs remain.
After merging with regression SNP LD, 1217474 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0155 (0.0013)
Lambda GC: 1.0847
Mean Chi^2: 1.1288
Intercept: 0.9884 (0.0059)
Ratio < 0 (usually indicates GC correction).
Analysis finished at Tue Jun 23 15:58:06 2020
Total time elapsed: 2.0m:46.81s
{
"af_correlation": 0.9622,
"inflation_factor": 0.9028,
"mean_EFFECT": -0.0253,
"n": 482730,
"n_snps": 17891936,
"n_clumped_hits": 23,
"n_p_sig": 3530,
"n_mono": 0,
"n_ns": 0,
"n_mac": 2171844,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 0,
"n_miss_AF_reference": 2582376,
"n_est": 379185.3044,
"ratio_se_n": 0.8863,
"mean_diff": 0.0239,
"ratio_diff": 450.6671,
"sd_y_est1": 19.7372,
"sd_y_est2": 17.4928,
"r2_sum1": 0.2059,
"r2_sum2": 0.0005,
"r2_sum3": 0.0007,
"r2_sum4": 0.0027,
"ldsc_nsnp_merge_refpanel_ld": 1217474,
"ldsc_nsnp_merge_regression_ld": 1217474,
"ldsc_observed_scale_h2_beta": 0.0155,
"ldsc_observed_scale_h2_se": 0.0013,
"ldsc_intercept_beta": 0.9884,
"ldsc_intercept_se": 0.0059,
"ldsc_lambda_gc": 1.0847,
"ldsc_mean_chisq": 1.1288,
"ldsc_ratio": -0.0901
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | FALSE |
n | FALSE |
is_snpid_non_unique | TRUE |
mean_EFFECT_nonfinite | FALSE |
mean_EFFECT_05 | FALSE |
mean_EFFECT_01 | FALSE |
mean_chisq | FALSE |
n_p_sig | TRUE |
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 | 45 | 0.9999975 | 3 | 64 | 0 | 17530232 | 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 | 8.625208e+00 | 5.761533e+00 | 1.000 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▃▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.910828e+07 | 5.617392e+07 | 173.000 | 3.305852e+07 | 6.982141e+07 | 1.147497e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | -2.534450e-02 | 7.009912e-01 | -5.000 | -1.295000e-01 | -5.100000e-03 | 6.650000e-02 | 5.000000e+00 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 5.109780e-01 | 1.296699e+00 | 0.016 | 3.680000e-02 | 2.241000e-01 | 6.792000e-01 | 1.491830e+03 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 5.159013e-01 | 2.825639e-01 | 0.000 | 2.775000e-01 | 5.216005e-01 | 7.582999e-01 | 1.000000e+00 | ▆▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 5.159015e-01 | 2.825645e-01 | 0.000 | 2.774851e-01 | 5.215619e-01 | 7.583165e-01 | 1.000000e+00 | ▆▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | 1.188529e-01 | 2.215974e-01 | 0.001 | 2.100000e-03 | 8.400000e-03 | 1.147000e-01 | 9.990000e-01 | ▇▁▁▁▁ |
numeric | AF_reference | 2582376 | 0.8556682 | NA | NA | NA | NA | NA | 1.379419e-01 | 2.248656e-01 | 0.000 | 1.797100e-03 | 2.436100e-02 | 1.701280e-01 | 1.000000e+00 | ▇▁▁▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | 1.998644e+05 | 2.299328e+05 | 528.000 | 3.443000e+03 | 1.151800e+04 | 4.686920e+05 | 4.827300e+05 | ▇▁▁▁▆ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 54591 | rs561234294 | A | G | 0.6797 | 0.8869 | 0.4435004 | 0.4434519 | 0.0062 | 0.0035942 | 999 |
1 | 54676 | rs2462492 | C | T | -0.0996 | 0.0656 | 0.1287001 | 0.1289406 | 0.3166 | NA | 2137 |
1 | 79188 | rs534350410 | G | T | 0.6704 | 0.8795 | 0.4458995 | 0.4459100 | 0.0062 | 0.0035942 | 999 |
1 | 82994 | rs574556077 | A | G | -1.2614 | 1.8502 | 0.4954000 | 0.4953881 | 0.0016 | 0.0019968 | 999 |
1 | 86028 | rs114608975 | T | C | 0.2158 | 0.1222 | 0.0774497 | 0.0774030 | 0.0655 | 0.0277556 | 2137 |
1 | 90231 | rs553304094 | C | A | -1.7603 | 1.8868 | 0.3508003 | 0.3508431 | 0.0017 | 0.0037939 | 999 |
1 | 91536 | rs6702460 | G | T | -0.1040 | 0.0625 | 0.0962698 | 0.0961124 | 0.3872 | 0.4207270 | 2137 |
1 | 234313 | rs8179466 | C | T | -0.1138 | 0.1413 | 0.4205000 | 0.4206012 | 0.0475 | NA | 2137 |
1 | 534192 | rs6680723 | C | T | -0.0316 | 0.0771 | 0.6815002 | 0.6819106 | 0.1804 | NA | 2137 |
1 | 544584 | rs576404767 | C | T | -0.6397 | 2.0828 | 0.7586999 | 0.7587409 | 0.0018 | 0.0003994 | 938 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51231424 | rs539541647 | A | G | -1.1451 | 1.2784 | 0.3704000 | 0.3703975 | 0.0015 | 0.0011981 | 3167 |
22 | 51232488 | rs376461333 | A | G | 0.1271 | 0.1670 | 0.4466003 | 0.4466106 | 0.0200 | NA | 11518 |
22 | 51233336 | rs1322471824 | A | G | -0.3659 | 2.4898 | 0.8832001 | 0.8831639 | 0.0011 | NA | 879 |
22 | 51234048 | rs141330630 | T | C | -0.3709 | 0.7974 | 0.6418004 | 0.6418336 | 0.0069 | 0.0095847 | 879 |
22 | 51234159 | rs8138356 | T | A | -0.9937 | 1.7318 | 0.5660998 | 0.5661058 | 0.0016 | 0.0215655 | 919 |
22 | 51234163 | rs192982090 | G | A | -1.5364 | 1.7089 | 0.3685997 | 0.3686218 | 0.0014 | 0.0007987 | 964 |
22 | 51234199 | rs6010092 | T | C | 0.1478 | 1.9246 | 0.9388000 | 0.9387865 | 0.0020 | 0.0313498 | 794 |
22 | 51237063 | rs3896457 | T | C | 0.0108 | 0.0457 | 0.8132001 | 0.8131814 | 0.2937 | 0.2050720 | 11518 |
22 | 51238513 | rs1569214665 | C | G | -1.8077 | 1.9812 | 0.3614997 | 0.3615441 | 0.0011 | NA | 938 |
22 | 51239586 | rs535432390 | T | G | -0.2659 | 0.3816 | 0.4859001 | 0.4859261 | 0.0036 | 0.0001997 | 11518 |
1 54591 rs561234294 A G . PASS AF=0.0062 ES:SE:LP:AF:SS:NC:ID 0.6797:0.8869:0.353106:0.0062:999:527:rs561234294
1 54676 rs2462492 C T . PASS AF=0.3166 ES:SE:LP:AF:SS:NC:ID -0.0996:0.0656:0.890421:0.3166:2137:1169:rs2462492
1 79188 rs534350410 G T . PASS AF=0.0062 ES:SE:LP:AF:SS:NC:ID 0.6704:0.8795:0.350763:0.0062:999:527:rs534350410
1 82994 rs574556077 A G . PASS AF=0.0016 ES:SE:LP:AF:SS:NC:ID -1.2614:1.8502:0.305044:0.0016:999:527:rs574556077
1 86028 rs114608975 T C . PASS AF=0.0655 ES:SE:LP:AF:SS:NC:ID 0.2158:0.1222:1.11098:0.0655:2137:1169:rs114608975
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1 91536 rs1251109649 G T . PASS AF=0.3872 ES:SE:LP:AF:SS:NC:ID -0.104:0.0625:1.01651:0.3872:2137:1169:rs1251109649
1 234313 rs8179466 C T . PASS AF=0.0475 ES:SE:LP:AF:SS:NC:ID -0.1138:0.1413:0.376234:0.0475:2137:1169:rs8179466
1 534192 rs6680723 C T . PASS AF=0.1804 ES:SE:LP:AF:SS:NC:ID -0.0316:0.0771:0.166534:0.1804:2137:1169:rs6680723
1 544584 rs576404767 C T . PASS AF=0.0018 ES:SE:LP:AF:SS:NC:ID -0.6397:2.0828:0.11993:0.0018:938:476:rs576404767
1 546697 rs12025928 A G . PASS AF=0.9244 ES:SE:LP:AF:SS:NC:ID -0.0212:0.116:0.0679323:0.9244:2137:1169:rs12025928
1 565196 rs139723294 T C . PASS AF=0.0037 ES:SE:LP:AF:SS:NC:ID 0.0096:0.9084:0.00366348:0.0037:1487:582:rs139723294
1 567006 rs565235853 G T . PASS AF=0.0028 ES:SE:LP:AF:SS:NC:ID 0.0357:0.7092:0.0178193:0.0028:4308:2447:rs565235853
1 570161 rs572999760 G A . PASS AF=0.001 ES:SE:LP:AF:SS:NC:ID 3.5709:8.9314:0.161592:0.001:919:620:rs572999760
1 603482 rs865926247 T C . PASS AF=0.0021 ES:SE:LP:AF:SS:NC:ID -0.618:1.5999:0.155336:0.0021:919:620:rs865926247
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1 615330 rs1275267063 C T . PASS AF=0.0013 ES:SE:LP:AF:SS:NC:ID 0.5173:2.0269:0.0977251:0.0013:919:620:rs1275267063
1 693731 rs12238997 A G . PASS AF=0.1206 ES:SE:LP:AF:SS:NC:ID 0.0182:0.0504:0.143694:0.1206:12776:7417:rs12238997
1 701131 rs185335630 A C . PASS AF=0.0036 ES:SE:LP:AF:SS:NC:ID 0.9666:1.3292:0.33059:0.0036:938:476:rs185335630
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1 706368 rs963699400 A G . PASS AF=0.5054 ES:SE:LP:AF:SS:NC:ID -0.0963:0.0837:0.602929:0.5054:3344:1678:rs963699400
1 710445 rs1334659872 A G . PASS AF=0.0045 ES:SE:LP:AF:SS:NC:ID -0.0953:0.6431:0.0544822:0.0045:2406:1202:rs1334659872
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1 713977 rs74512038 C T . PASS AF=0.0032 ES:SE:LP:AF:SS:NC:ID 0.5202:0.9403:0.236497:0.0032:2901:1772:rs74512038
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1 715585 rs897133337 A T . PASS AF=0.0012 ES:SE:LP:AF:SS:NC:ID -1.1187:2.4166:0.191519:0.0012:919:620:rs897133337
1 717474 rs141784362 C T . PASS AF=0.0081 ES:SE:LP:AF:SS:NC:ID 0.0438:0.308:0.0520764:0.0081:6787:3788:rs141784362
1 717485 rs12184279 C A . PASS AF=0.0337 ES:SE:LP:AF:SS:NC:ID -0.0084:0.109:0.0273807:0.0337:12776:7417:rs12184279
1 717587 rs144155419 G A . PASS AF=0.0136 ES:SE:LP:AF:SS:NC:ID -0.0099:0.1371:0.0257647:0.0136:463162:23259:rs144155419
1 718624 rs777092529 C G . PASS AF=0.0023 ES:SE:LP:AF:SS:NC:ID -0.863:1.1423:0.346884:0.0023:1883:1389:rs777092529
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1 720583 rs551231909 G A . PASS AF=0.006 ES:SE:LP:AF:SS:NC:ID 0.0379:0.3868:0.0352691:0.006:5849:3312:rs551231909
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1 721538 rs569523401 A C . PASS AF=0.001 ES:SE:LP:AF:SS:NC:ID 2.7463:1.9236:0.814175:0.001:1487:582:rs569523401
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1 722980 rs114222710 C T . PASS AF=0.0082 ES:SE:LP:AF:SS:NC:ID 0.0196:0.3161:0.0219565:0.0082:5849:3312:rs114222710
1 723345 rs546176432 A C . PASS AF=0.0011 ES:SE:LP:AF:SS:NC:ID -1.5948:2.5977:0.26817:0.0011:1487:582:rs546176432
1 723891 rs2977670 G C . PASS AF=0.9556 ES:SE:LP:AF:SS:NC:ID -0.0139:0.0926:0.0552213:0.9556:12776:7417:rs2977670
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