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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/4179b847-0a94-4f72-b90a-e14e2774d1d8/call-vcf/inputs/-261044506/upload.txt.gz --id ieu-b-4826 --json /data/cromwell-executions/qc/4179b847-0a94-4f72-b90a-e14e2774d1d8/call-vcf/inputs/-261044506/ieu-b-4826_data.json --ref /data/cromwell-executions/qc/4179b847-0a94-4f72-b90a-e14e2774d1d8/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/4179b847-0a94-4f72-b90a-e14e2774d1d8/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-4826/ieu-b-4826.vcf.gz --alias alias.txt; 1.3.0",
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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/4179b847-0a94-4f72-b90a-e14e2774d1d8/call-ldsc/inputs/-261044506/ieu-b-4826.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4826/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Wed Jan 5 08:50:33 2022
Reading summary statistics from /data/cromwell-executions/qc/4179b847-0a94-4f72-b90a-e14e2774d1d8/call-ldsc/inputs/-261044506/ieu-b-4826.vcf.gz ...
Read summary statistics for 7227274 SNPs.
Dropped 35625 SNPs with duplicated rs numbers.
Reading reference panel LD Score from /data/ref/eur_w_ld_chr/[1-22] ... (ldscore_fromlist)
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] ... (ldscore_fromlist)
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1182558 SNPs remain.
After merging with regression SNP LD, 1182558 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0513 (0.0217)
Lambda GC: 1.0819
Mean Chi^2: 1.094
Intercept: 1.0696 (0.0064)
Ratio: 0.7403 (0.0678)
Analysis finished at Wed Jan 5 08:52:13 2022
Total time elapsed: 1.0m:39.91s
{
"af_correlation": "NA",
"inflation_factor": 1.0782,
"mean_EFFECT": -0.0032,
"n": 24784,
"n_snps": 7227329,
"n_clumped_hits": 4,
"n_p_sig": 270,
"n_mono": 0,
"n_ns": 252547,
"n_mac": 0,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 7227329,
"n_miss_AF_reference": 146003,
"n_est": "NA",
"ratio_se_n": "NA",
"mean_diff": "NaN",
"ratio_diff": "NaN",
"sd_y_est1": "NaN",
"sd_y_est2": "NA",
"r2_sum1": 0,
"r2_sum2": 0,
"r2_sum3": 0,
"r2_sum4": 0,
"ldsc_nsnp_merge_refpanel_ld": 1182558,
"ldsc_nsnp_merge_regression_ld": 1182558,
"ldsc_observed_scale_h2_beta": 0.0513,
"ldsc_observed_scale_h2_se": 0.0217,
"ldsc_intercept_beta": 1.0696,
"ldsc_intercept_se": 0.0064,
"ldsc_lambda_gc": 1.0819,
"ldsc_mean_chisq": 1.094,
"ldsc_ratio": 0.7404
}
name | value |
---|---|
af_correlation | NA |
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 | FALSE |
miss_EFFECT | FALSE |
miss_SE | FALSE |
miss_PVAL | FALSE |
ldsc_ratio | TRUE |
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 | logical.mean | logical.count | numeric.mean | numeric.sd | numeric.p0 | numeric.p25 | numeric.p50 | numeric.p75 | numeric.p100 | numeric.hist |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
character | ID | 13 | 0.9999982 | 3 | 58 | 0 | 7227213 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 43 | 0 | 14891 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 44 | 0 | 5406 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | AF | 7227329 | 0.0000000 | NA | NA | NA | NA | NA | NaN | : | NA | NA | NA | NA | NA | NA | NA | NA |
numeric | CHROM | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 8.649468e+00 | 5.755541e+00 | 1.0000e+00 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 7.899276e+07 | 5.639184e+07 | 3.0200e+02 | 3.266801e+07 | 6.969762e+07 | 1.147510e+08 | 2.492223e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -3.180100e-03 | 1.306916e-01 | -1.2761e+00 | -7.070000e-02 | -2.600000e-03 | 6.510000e-02 | 1.373100e+00 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.127885e-01 | 5.696400e-02 | 6.0300e-02 | 7.040000e-02 | 8.800000e-02 | 1.369000e-01 | 4.327000e-01 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.874716e-01 | 2.919819e-01 | 0.0000e+00 | 2.319001e-01 | 4.836999e-01 | 7.403993e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.874717e-01 | 2.919819e-01 | 0.0000e+00 | 2.318557e-01 | 4.837392e-01 | 7.404196e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF_reference | 146003 | 0.9797985 | NA | NA | NA | NA | NA | NA | NA | 2.851437e-01 | 2.502800e-01 | 1.9970e-04 | 7.987220e-02 | 2.064700e-01 | 4.404950e-01 | 1.000000e+00 | ▇▃▂▂▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.250942e+04 | 2.731422e+03 | 1.5016e+04 | 2.011000e+04 | 2.409200e+04 | 2.478400e+04 | 2.478400e+04 | ▁▃▁▁▇ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 797440 | rs58013264 | T | C | 0.0230 | 0.0998 | 0.8179000 | 0.8177336 | NA | 0.189497 | 22027 |
1 | 798400 | rs10900604 | A | G | 0.0388 | 0.0816 | 0.6343004 | 0.6344376 | NA | 0.410543 | 22480 |
1 | 798959 | rs11240777 | G | A | 0.0392 | 0.0816 | 0.6312000 | 0.6309486 | NA | 0.409944 | 22480 |
1 | 801467 | rs61768212 | G | C | 0.0188 | 0.0997 | 0.8499999 | 0.8504332 | NA | 0.193091 | 22027 |
1 | 804759 | rs7526310 | C | T | 0.0166 | 0.0998 | 0.8677999 | 0.8678952 | NA | 0.193890 | 22027 |
1 | 808223 | rs4951933 | G | C | -0.0467 | 0.0877 | 0.5942005 | 0.5943817 | NA | 0.452077 | 17930 |
1 | 808631 | rs11240779 | G | A | -0.0358 | 0.0798 | 0.6535006 | 0.6537047 | NA | 0.453474 | 21674 |
1 | 808928 | rs11240780 | C | T | -0.0338 | 0.0798 | 0.6713995 | 0.6718875 | NA | 0.452276 | 21674 |
1 | 845274 | rs112856858 | G | T | -0.1493 | 0.0881 | 0.0903296 | 0.0901390 | NA | 0.374002 | 17930 |
1 | 845635 | rs117086422 | C | T | -0.1406 | 0.0802 | 0.0794694 | 0.0795819 | NA | 0.158546 | 22480 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51172460 | rs5770824 | T | C | -0.0474 | 0.2749 | 0.8631999 | 0.8631024 | NA | 0.0684904 | 17930 |
22 | 51177257 | rs73174437 | C | T | 0.0857 | 0.2131 | 0.6877000 | 0.6875673 | NA | 0.0091853 | 17930 |
22 | 51178607 | rs6010067 | G | C | -0.1635 | 0.2788 | 0.5576003 | 0.5575786 | NA | 0.0814696 | 17930 |
22 | 51180878 | rs6010069 | A | G | 0.0201 | 0.1014 | 0.8429001 | 0.8428691 | NA | 0.1589460 | 17930 |
22 | 51180959 | rs6010070 | A | G | 0.0214 | 0.1013 | 0.8324999 | 0.8326893 | NA | 0.2056710 | 17930 |
22 | 51181685 | rs34756634 | G | A | 0.0621 | 0.1108 | 0.5748996 | 0.5751594 | NA | 0.7118610 | 17930 |
22 | 51181687 | rs9616955 | A | T | 0.1793 | 0.1611 | 0.2657003 | 0.2657199 | NA | 0.0485224 | 17930 |
22 | 51181759 | rs13056621 | A | G | 0.1796 | 0.1021 | 0.0784603 | 0.0785674 | NA | 0.6761180 | 23216 |
22 | 51182090 | rs28516879 | G | A | 0.0485 | 0.1354 | 0.7204005 | 0.7201952 | NA | 0.0467252 | 22763 |
22 | 51185848 | rs3865764 | G | A | 0.3308 | 0.1753 | 0.0590895 | 0.0591535 | NA | 0.9776360 | 17930 |
1 797440 rs58013264 T C . PASS . ES:SE:LP:SS:ID 0.023:0.0998:0.0872998:22027:rs58013264
1 798400 rs10900604 A G . PASS . ES:SE:LP:SS:ID 0.0388:0.0816:0.197705:22480:rs10900604
1 798959 rs11240777 G A . PASS . ES:SE:LP:SS:ID 0.0392:0.0816:0.199833:22480:rs11240777
1 801467 rs61768212 G C . PASS . ES:SE:LP:SS:ID 0.0188:0.0997:0.0705811:22027:rs61768212
1 804759 rs7526310 C T . PASS . ES:SE:LP:SS:ID 0.0166:0.0998:0.0615804:22027:rs7526310
1 808223 rs1557576983 G C . PASS . ES:SE:LP:SS:ID -0.0467:0.0877:0.226067:17930:rs1557576983
1 808631 rs11240779 G A . PASS . ES:SE:LP:SS:ID -0.0358:0.0798:0.184754:21674:rs11240779
1 808928 rs1247187939 C T . PASS . ES:SE:LP:SS:ID -0.0338:0.0798:0.173019:21674:rs1247187939
1 845274 rs1324283754 G T . PASS . ES:SE:LP:SS:ID -0.1493:0.0881:1.04417:17930:rs1324283754
1 845635 rs117086422 C T . PASS . ES:SE:LP:SS:ID -0.1406:0.0802:1.0998:22480:rs117086422
1 845938 rs57760052 G A . PASS . ES:SE:LP:SS:ID -0.1418:0.0796:1.12616:22480:rs57760052
1 846078 rs778265812 C T . PASS . ES:SE:LP:SS:ID -0.126:0.0831:0.88706:22480:rs778265812
1 846398 rs58781670 G A . PASS . ES:SE:LP:SS:ID -0.1397:0.0809:1.07603:22480:rs58781670
1 846808 rs4475691 C T . PASS . ES:SE:LP:SS:ID -0.1237:0.0828:0.868381:22480:rs4475691
1 846864 rs1269142199 G C . PASS . ES:SE:LP:SS:ID -0.126:0.0831:0.888066:22480:rs1269142199
1 847228 rs3905286 C T . PASS . ES:SE:LP:SS:ID -0.1163:0.0815:0.813326:22480:rs3905286
1 847491 rs1158719307 G A . PASS . ES:SE:LP:SS:ID -0.1238:0.0805:0.905529:22480:rs1158719307
1 848090 rs4246505 G A . PASS . ES:SE:LP:SS:ID -0.1335:0.0808:1.00599:22480:rs4246505
1 848445 rs1156895099 G A . PASS . ES:SE:LP:SS:ID -0.1209:0.0806:0.874194:22480:rs1156895099
1 848456 rs11507767 A G . PASS . ES:SE:LP:SS:ID -0.1207:0.0806:0.871924:22480:rs11507767
1 848738 rs3829741 C T . PASS . ES:SE:LP:SS:ID -0.1324:0.0808:0.994391:22480:rs3829741
1 850062 rs28723578 A T . PASS . ES:SE:LP:SS:ID -0.1219:0.0804:0.886725:22480:rs28723578
1 850123 rs28622257 C T . PASS . ES:SE:LP:SS:ID -0.13:0.0807:0.968996:22480:rs28622257
1 851190 rs28609852 G A . PASS . ES:SE:LP:SS:ID -0.1216:0.0805:0.883392:22480:rs28609852
1 851204 rs28552953 G C . PASS . ES:SE:LP:SS:ID -0.1043:0.0808:0.706416:22480:rs28552953
1 852664 rs28605311 C T . PASS . ES:SE:LP:SS:ID -0.1248:0.0815:0.90101:22480:rs28605311
1 852758 rs4970462 G C . PASS . ES:SE:LP:SS:ID -0.1243:0.0815:0.896196:22480:rs4970462
1 853239 rs4970380 A G . PASS . ES:SE:LP:SS:ID -0.1244:0.0815:0.896538:22480:rs4970380
1 854250 rs7537756 A G . PASS . ES:SE:LP:SS:ID -0.1156:0.0812:0.809949:22480:rs7537756
1 856436 rs34105146 TG T . PASS . ES:SE:LP:SS:ID -0.0907:0.0907:0.499078:17930:rs34105146
1 856476 rs4040605 A G . PASS . ES:SE:LP:SS:ID 0.0066:0.0686:0.0345631:22480:rs4040605
1 858040 rs4970460 C A . PASS . ES:SE:LP:SS:ID -0.1167:0.0794:0.848937:22480:rs4970460
1 858051 rs4970459 C T . PASS . ES:SE:LP:SS:ID -0.1172:0.0794:0.854493:22480:rs4970459
1 858801 rs7418179 A G . PASS . ES:SE:LP:SS:ID 0.1509:0.0766:1.31238:22480:rs7418179
1 859685 rs111572704 G A . PASS . ES:SE:LP:SS:ID -0.1256:0.0882:0.811916:17930:rs111572704
1 860416 rs61464428 G A . PASS . ES:SE:LP:SS:ID 0.146:0.0768:1.24253:22480:rs61464428
1 860461 rs57465118 G A . PASS . ES:SE:LP:SS:ID 0.1631:0.208:0.363412:17930:rs57465118
1 860521 rs57924093 C A . PASS . ES:SE:LP:SS:ID 0.1631:0.208:0.363412:17930:rs57924093
1 860688 rs60837925 G A . PASS . ES:SE:LP:SS:ID 0.1469:0.0768:1.2543:22480:rs60837925
1 861008 rs28521172 G C . PASS . ES:SE:LP:SS:ID 0.1631:0.208:0.363412:17930:rs28521172
1 861630 rs2879816 G A . PASS . ES:SE:LP:SS:ID 0.1484:0.0767:1.27417:22480:rs2879816
1 861808 rs13302982 A G . PASS . ES:SE:LP:SS:ID 0.1631:0.208:0.363412:17930:rs13302982
1 862093 rs1210451934 T C . PASS . ES:SE:LP:SS:ID 0.1645:0.2079:0.367847:17930:rs1210451934
1 862124 rs13303101 A G . PASS . ES:SE:LP:SS:ID 0.164:0.2078:0.366431:17930:rs13303101
1 862383 rs6680268 C T . PASS . ES:SE:LP:SS:ID 0.1622:0.208:0.361012:17930:rs6680268
1 862389 rs534606253 A G . PASS . ES:SE:LP:SS:ID 0.1631:0.208:0.363412:17930:rs534606253
1 862866 rs3892970 C T . PASS . ES:SE:LP:SS:ID 0.1373:0.0764:1.14158:22480:rs3892970
1 863124 rs4040604 G T . PASS . ES:SE:LP:SS:ID 0.1806:0.2081:0.413976:17930:rs4040604
1 864002 rs1806501 G C . PASS . ES:SE:LP:SS:ID -0.1499:0.0797:1.22062:22480:rs1806501
1 864938 rs1185651409 G A . PASS . ES:SE:LP:SS:ID 0.1577:0.0757:1.42852:22480:rs1185651409