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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/5e294b2a-d116-4b0c-8693-ed79a88f0d1a/call-vcf/inputs/-261044388/upload.txt.gz --id ieu-b-4860 --json /data/cromwell-executions/qc/5e294b2a-d116-4b0c-8693-ed79a88f0d1a/call-vcf/inputs/-261044388/ieu-b-4860_data.json --ref /data/cromwell-executions/qc/5e294b2a-d116-4b0c-8693-ed79a88f0d1a/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/5e294b2a-d116-4b0c-8693-ed79a88f0d1a/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-4860/ieu-b-4860.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/5e294b2a-d116-4b0c-8693-ed79a88f0d1a/call-ldsc/inputs/-261044388/ieu-b-4860.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4860/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Wed Jan 5 19:34:04 2022
Reading summary statistics from /data/cromwell-executions/qc/5e294b2a-d116-4b0c-8693-ed79a88f0d1a/call-ldsc/inputs/-261044388/ieu-b-4860.vcf.gz ...
Read summary statistics for 7986977 SNPs.
Dropped 39184 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, 1202971 SNPs remain.
After merging with regression SNP LD, 1202971 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0119 (0.0063)
Lambda GC: 1.0536
Mean Chi^2: 1.0477
Intercept: 1.0299 (0.0068)
Ratio: 0.6266 (0.1434)
Analysis finished at Wed Jan 5 19:35:45 2022
Total time elapsed: 1.0m:40.92s
{
"af_correlation": "NA",
"inflation_factor": 1.0388,
"mean_EFFECT": -0,
"n": 78007,
"n_snps": 7987053,
"n_clumped_hits": 0,
"n_p_sig": 0,
"n_mono": 0,
"n_ns": 285767,
"n_mac": 0,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 7987053,
"n_miss_AF_reference": 166434,
"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": 1202971,
"ldsc_nsnp_merge_regression_ld": 1202971,
"ldsc_observed_scale_h2_beta": 0.0119,
"ldsc_observed_scale_h2_se": 0.0063,
"ldsc_intercept_beta": 1.0299,
"ldsc_intercept_se": 0.0068,
"ldsc_lambda_gc": 1.0536,
"ldsc_mean_chisq": 1.0477,
"ldsc_ratio": 0.6268
}
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 | 26 | 0.9999967 | 3 | 58 | 0 | 7986884 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 43 | 0 | 16651 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 44 | 0 | 6034 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | AF | 7987053 | 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 | 8.646238e+00 | 5.754043e+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 | 7.884892e+07 | 5.635741e+07 | 3.0200e+02 | 3.246384e+07 | 6.941758e+07 | 1.146302e+08 | 2.492223e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -1.370000e-05 | 5.117500e-03 | -5.2800e-02 | -2.500000e-03 | 0.000000e+00 | 2.500000e-03 | 4.710000e-02 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.379300e-03 | 2.463800e-03 | 2.2000e-03 | 2.500000e-03 | 3.300000e-03 | 5.600000e-03 | 1.370000e-02 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.933516e-01 | 2.904518e-01 | 1.0000e-07 | 2.397000e-01 | 4.918005e-01 | 7.446994e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.934946e-01 | 2.905267e-01 | 1.0000e-07 | 2.404299e-01 | 4.904111e-01 | 7.456925e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF_reference | 166434 | 0.9791620 | NA | NA | NA | NA | NA | NA | NA | 2.642209e-01 | 2.522116e-01 | 0.0000e+00 | 5.670930e-02 | 1.783150e-01 | 4.125400e-01 | 1.000000e+00 | ▇▃▂▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 7.361196e+04 | 5.964515e+03 | 4.7002e+04 | 7.328200e+04 | 7.674700e+04 | 7.800700e+04 | 7.800700e+04 | ▁▁▂▁▇ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 797440 | rs58013264 | T | C | -0.0008 | 0.0036 | 0.8233000 | 0.8241409 | NA | 0.189497 | 68094 |
1 | 798400 | rs10900604 | A | G | 0.0008 | 0.0030 | 0.7842003 | 0.7897258 | NA | 0.410543 | 68094 |
1 | 798959 | rs11240777 | G | A | 0.0009 | 0.0029 | 0.7459007 | 0.7562987 | NA | 0.409944 | 70768 |
1 | 801467 | rs61768212 | G | C | -0.0007 | 0.0036 | 0.8483001 | 0.8458279 | NA | 0.193091 | 68094 |
1 | 804759 | rs7526310 | C | T | -0.0009 | 0.0036 | 0.8100000 | 0.8025873 | NA | 0.193890 | 68094 |
1 | 808223 | rs4951933 | G | C | 0.0010 | 0.0031 | 0.7393992 | 0.7470129 | NA | 0.452077 | 62455 |
1 | 808631 | rs11240779 | G | A | 0.0003 | 0.0029 | 0.9305999 | 0.9176072 | NA | 0.453474 | 68094 |
1 | 808928 | rs11240780 | C | T | 0.0002 | 0.0029 | 0.9434001 | 0.9450171 | NA | 0.452276 | 68094 |
1 | 845274 | rs112856858 | G | T | 0.0017 | 0.0032 | 0.5863001 | 0.5952455 | NA | 0.374002 | 62455 |
1 | 845635 | rs117086422 | C | T | 0.0012 | 0.0029 | 0.6676994 | 0.6790256 | NA | 0.158546 | 70768 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51218377 | rs2519461 | G | C | -0.0017 | 0.0051 | 0.7467995 | 0.7388827 | NA | 0.0826677 | 52190 |
22 | 51219006 | rs28729663 | G | A | -0.0070 | 0.0041 | 0.0845805 | 0.0877631 | NA | 0.2052720 | 49516 |
22 | 51219387 | rs9616832 | T | C | -0.0021 | 0.0051 | 0.6766997 | 0.6805119 | NA | 0.0654952 | 52190 |
22 | 51219704 | rs147475742 | G | A | -0.0102 | 0.0071 | 0.1540001 | 0.1508261 | NA | 0.0473243 | 49516 |
22 | 51221190 | rs369304721 | G | A | -0.0111 | 0.0063 | 0.0785597 | 0.0780854 | NA | NA | 49516 |
22 | 51221731 | rs115055839 | T | C | -0.0023 | 0.0052 | 0.6560002 | 0.6582666 | NA | 0.0625000 | 52190 |
22 | 51222100 | rs114553188 | G | T | -0.0098 | 0.0058 | 0.0896107 | 0.0910939 | NA | 0.0880591 | 52190 |
22 | 51223637 | rs375798137 | G | A | -0.0102 | 0.0058 | 0.0791899 | 0.0786420 | NA | 0.0788738 | 52190 |
22 | 51229805 | rs9616985 | T | C | -0.0019 | 0.0052 | 0.7142003 | 0.7148243 | NA | 0.0730831 | 52190 |
22 | 51237063 | rs3896457 | T | C | -0.0010 | 0.0031 | 0.7362003 | 0.7470129 | NA | 0.2050720 | 49516 |
1 797440 rs58013264 T C . PASS . ES:SE:LP:SS:ID -0.0008:0.0036:0.0844419:68094:rs58013264
1 798400 rs10900604 A G . PASS . ES:SE:LP:SS:ID 0.0008:0.003:0.105573:68094:rs10900604
1 798959 rs11240777 G A . PASS . ES:SE:LP:SS:ID 0.0009:0.0029:0.127319:70768:rs11240777
1 801467 rs61768212 G C . PASS . ES:SE:LP:SS:ID -0.0007:0.0036:0.0714505:68094:rs61768212
1 804759 rs7526310 C T . PASS . ES:SE:LP:SS:ID -0.0009:0.0036:0.091515:68094:rs7526310
1 808223 rs1557576983 G C . PASS . ES:SE:LP:SS:ID 0.001:0.0031:0.131121:62455:rs1557576983
1 808631 rs11240779 G A . PASS . ES:SE:LP:SS:ID 0.0003:0.0029:0.031237:68094:rs11240779
1 808928 rs1247187939 C T . PASS . ES:SE:LP:SS:ID 0.0002:0.0029:0.0253041:68094:rs1247187939
1 845274 rs1324283754 G T . PASS . ES:SE:LP:SS:ID 0.0017:0.0032:0.23188:62455:rs1324283754
1 845635 rs117086422 C T . PASS . ES:SE:LP:SS:ID 0.0012:0.0029:0.175419:70768:rs117086422
1 845938 rs57760052 G A . PASS . ES:SE:LP:SS:ID 0.0011:0.0029:0.147093:70768:rs57760052
1 846078 rs778265812 C T . PASS . ES:SE:LP:SS:ID 0.0023:0.003:0.360215:70768:rs778265812
1 846398 rs58781670 G A . PASS . ES:SE:LP:SS:ID 0.0003:0.0029:0.0420098:70768:rs58781670
1 846465 rs60454217 C T . PASS . ES:SE:LP:SS:ID -0.0142:0.0092:0.915781:68094:rs60454217
1 846543 rs79396034 G T . PASS . ES:SE:LP:SS:ID -0.0125:0.0095:0.726536:68094:rs79396034
1 846808 rs4475691 C T . PASS . ES:SE:LP:SS:ID 0.0021:0.003:0.323124:70768:rs4475691
1 846864 rs1269142199 G C . PASS . ES:SE:LP:SS:ID 0.0022:0.003:0.342275:70768:rs1269142199
1 847228 rs3905286 C T . PASS . ES:SE:LP:SS:ID 0.0009:0.0029:0.116566:70768:rs3905286
1 847491 rs1158719307 G A . PASS . ES:SE:LP:SS:ID 0.0028:0.0029:0.486516:70768:rs1158719307
1 848090 rs4246505 G A . PASS . ES:SE:LP:SS:ID 0.003:0.0029:0.524619:70768:rs4246505
1 848445 rs1156895099 G A . PASS . ES:SE:LP:SS:ID 0.0027:0.0029:0.454817:70768:rs1156895099
1 848456 rs11507767 A G . PASS . ES:SE:LP:SS:ID 0.0028:0.0029:0.467373:70768:rs11507767
1 848738 rs3829741 C T . PASS . ES:SE:LP:SS:ID 0.003:0.0029:0.520281:70768:rs3829741
1 850062 rs28723578 A T . PASS . ES:SE:LP:SS:ID 0.0027:0.0029:0.45705:70768:rs28723578
1 850123 rs28622257 C T . PASS . ES:SE:LP:SS:ID 0.0029:0.0029:0.501001:70768:rs28622257
1 851190 rs28609852 G A . PASS . ES:SE:LP:SS:ID 0.0026:0.0029:0.443336:70768:rs28609852
1 851204 rs28552953 G C . PASS . ES:SE:LP:SS:ID 0.0029:0.0028:0.507938:70768:rs28552953
1 852664 rs28605311 C T . PASS . ES:SE:LP:SS:ID 0.0033:0.0029:0.593801:70768:rs28605311
1 852758 rs4970462 G C . PASS . ES:SE:LP:SS:ID 0.0032:0.0029:0.571379:70768:rs4970462
1 853239 rs4970380 A G . PASS . ES:SE:LP:SS:ID 0.0033:0.0029:0.579055:70768:rs4970380
1 853805 rs3748591 C T . PASS . ES:SE:LP:SS:ID -0.0149:0.0083:1.13071:68094:rs3748591
1 854250 rs7537756 A G . PASS . ES:SE:LP:SS:ID 0.0028:0.0029:0.483332:70768:rs7537756
1 854429 rs72902552 G A . PASS . ES:SE:LP:SS:ID -0.0152:0.0083:1.17076:68094:rs72902552
1 856436 rs34105146 TG T . PASS . ES:SE:LP:SS:ID 0.0048:0.0032:0.872247:62455:rs34105146
1 856476 rs4040605 A G . PASS . ES:SE:LP:SS:ID 0.0042:0.0025:1.00436:68094:rs4040605
1 857177 rs386627408 T C . PASS . ES:SE:LP:SS:ID -0.014:0.0081:1.07816:68094:rs386627408
1 858040 rs4970460 C A . PASS . ES:SE:LP:SS:ID 0.0036:0.003:0.646084:68094:rs4970460
1 858051 rs4970459 C T . PASS . ES:SE:LP:SS:ID 0.0038:0.003:0.68382:68094:rs4970459
1 858801 rs7418179 A G . PASS . ES:SE:LP:SS:ID -0.0012:0.0029:0.175549:68094:rs7418179
1 859404 rs71509444 C G . PASS . ES:SE:LP:SS:ID 0.0105:0.009:0.607655:62455:rs71509444
1 859685 rs111572704 G A . PASS . ES:SE:LP:SS:ID 0.0032:0.0031:0.508778:62455:rs111572704
1 859690 rs71509445 C G . PASS . ES:SE:LP:SS:ID 0.014:0.0095:0.848018:62455:rs71509445
1 859701 rs71509446 C G . PASS . ES:SE:LP:SS:ID 0.014:0.0095:0.848018:62455:rs71509446
1 859913 rs1187056171 A G . PASS . ES:SE:LP:SS:ID 0.02:0.0089:1.6038:68094:rs1187056171
1 860416 rs61464428 G A . PASS . ES:SE:LP:SS:ID -0.0015:0.0029:0.225775:68094:rs61464428
1 860461 rs57465118 G A . PASS . ES:SE:LP:SS:ID 0.0149:0.0079:1.21645:68094:rs57465118
1 860521 rs57924093 C A . PASS . ES:SE:LP:SS:ID 0.0149:0.0079:1.21645:68094:rs57924093
1 860688 rs60837925 G A . PASS . ES:SE:LP:SS:ID -0.0015:0.0029:0.221053:68094:rs60837925
1 860854 rs57816555 T C . PASS . ES:SE:LP:SS:ID 0.0088:0.0103:0.402963:62455:rs57816555
1 861008 rs28521172 G C . PASS . ES:SE:LP:SS:ID 0.0151:0.0079:1.24094:68094:rs28521172