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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/d4f083fe-3b19-45af-8f09-c216b5e2ac2e/call-vcf/inputs/-261044476/upload.txt.gz --id ieu-b-4835 --json /data/cromwell-executions/qc/d4f083fe-3b19-45af-8f09-c216b5e2ac2e/call-vcf/inputs/-261044476/ieu-b-4835_data.json --ref /data/cromwell-executions/qc/d4f083fe-3b19-45af-8f09-c216b5e2ac2e/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/d4f083fe-3b19-45af-8f09-c216b5e2ac2e/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-4835/ieu-b-4835.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/d4f083fe-3b19-45af-8f09-c216b5e2ac2e/call-ldsc/inputs/-261044476/ieu-b-4835.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4835/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Wed Jan 5 09:56:29 2022
Reading summary statistics from /data/cromwell-executions/qc/d4f083fe-3b19-45af-8f09-c216b5e2ac2e/call-ldsc/inputs/-261044476/ieu-b-4835.vcf.gz ...
Read summary statistics for 7209997 SNPs.
Dropped 19875 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, 1201526 SNPs remain.
After merging with regression SNP LD, 1201526 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0361 (0.0076)
Lambda GC: 1.0616
Mean Chi^2: 1.0578
Intercept: 1.0199 (0.0061)
Ratio: 0.3442 (0.1054)
Analysis finished at Wed Jan 5 09:58:10 2022
Total time elapsed: 1.0m:41.23s
{
"af_correlation": "NA",
"inflation_factor": 1.0523,
"mean_EFFECT": -0.0001,
"n": 54986,
"n_snps": 7210025,
"n_clumped_hits": 0,
"n_p_sig": 0,
"n_mono": 0,
"n_ns": 0,
"n_mac": 0,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 7210025,
"n_miss_AF_reference": 48695,
"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": 1201526,
"ldsc_nsnp_merge_regression_ld": 1201526,
"ldsc_observed_scale_h2_beta": 0.0361,
"ldsc_observed_scale_h2_se": 0.0076,
"ldsc_intercept_beta": 1.0199,
"ldsc_intercept_se": 0.0061,
"ldsc_lambda_gc": 1.0616,
"ldsc_mean_chisq": 1.0578,
"ldsc_ratio": 0.3443
}
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 | 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 | logical.mean | logical.count | numeric.mean | numeric.sd | numeric.p0 | numeric.p25 | numeric.p50 | numeric.p75 | numeric.p100 | numeric.hist |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
character | ID | 11 | 0.9999985 | 3 | 58 | 0 | 7209987 | 0 | NA | NA | 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 | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | AF | 7210025 | 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 | 8.638468e+00 | 5.748373e+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 | 7.887007e+07 | 5.638044e+07 | 8.2800e+02 | 3.243537e+07 | 6.946602e+07 | 1.147268e+08 | 2.492223e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -5.160000e-05 | 1.316610e-02 | -1.3740e-01 | -6.400000e-03 | 0.000000e+00 | 6.300000e-03 | 1.489000e-01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.118370e-02 | 6.554500e-03 | 5.0000e-03 | 6.300000e-03 | 8.300000e-03 | 1.380000e-02 | 3.900000e-02 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.920149e-01 | 2.906830e-01 | 1.0000e-07 | 2.380998e-01 | 4.890002e-01 | 7.439008e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.920193e-01 | 2.906992e-01 | 1.0000e-07 | 2.379417e-01 | 4.887441e-01 | 7.432246e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF_reference | 48695 | 0.9932462 | NA | NA | NA | NA | NA | NA | NA | 2.663141e-01 | 2.522568e-01 | 1.9970e-04 | 5.930510e-02 | 1.809110e-01 | 4.147360e-01 | 1.000000e+00 | ▇▃▂▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 5.094767e+04 | 5.507060e+03 | 3.1253e+04 | 5.066500e+04 | 5.310300e+04 | 5.473200e+04 | 5.498600e+04 | ▁▁▁▁▇ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 693731 | rs12238997 | A | G | -0.0013 | 0.0112 | 0.9108000 | 0.9075959 | NA | 0.141773 | 32560 |
1 | 731718 | rs142557973 | T | C | -0.0021 | 0.0109 | 0.8477000 | 0.8472248 | NA | 0.154353 | 32560 |
1 | 734349 | rs141242758 | T | C | -0.0018 | 0.0110 | 0.8729000 | 0.8700174 | NA | 0.152556 | 32560 |
1 | 736289 | rs79010578 | T | A | -0.0034 | 0.0108 | 0.7500997 | 0.7529023 | NA | 0.139577 | 32848 |
1 | 752566 | rs3094315 | G | A | 0.0007 | 0.0100 | 0.9425001 | 0.9441937 | NA | 0.718251 | 32520 |
1 | 753541 | rs2073813 | G | A | 0.0018 | 0.0106 | 0.8655001 | 0.8651585 | NA | 0.301917 | 33139 |
1 | 766007 | rs61768174 | A | C | 0.0027 | 0.0115 | 0.8138000 | 0.8143775 | NA | 0.091254 | 32560 |
1 | 768253 | rs2977608 | A | C | 0.0021 | 0.0085 | 0.8088999 | 0.8048627 | NA | 0.489417 | 32848 |
1 | 768448 | rs12562034 | G | A | -0.0095 | 0.0121 | 0.4331996 | 0.4323809 | NA | 0.191893 | 32848 |
1 | 769223 | rs60320384 | C | G | -0.0010 | 0.0106 | 0.9259000 | 0.9248394 | NA | 0.191294 | 32879 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51198906 | rs6010079 | G | A | 0.0023 | 0.0139 | 0.8713000 | 0.8685759 | NA | 0.0421326 | 34336 |
22 | 51202748 | rs9616963 | A | G | -0.0001 | 0.0139 | 0.9966000 | 0.9942599 | NA | 0.0391374 | 34336 |
22 | 51208537 | rs72619593 | G | A | 0.0110 | 0.0112 | 0.3221002 | 0.3260295 | NA | 0.1142170 | 32848 |
22 | 51208568 | rs148425445 | G | T | -0.0201 | 0.0155 | 0.1941999 | 0.1947089 | NA | 0.1160140 | 36530 |
22 | 51210289 | rs112565862 | C | T | -0.0012 | 0.0114 | 0.9192000 | 0.9161670 | NA | 0.1018370 | 32848 |
22 | 51211031 | rs9616968 | A | G | 0.0016 | 0.0142 | 0.9097999 | 0.9102874 | NA | 0.0373403 | 34336 |
22 | 51213613 | rs34726907 | C | T | -0.0096 | 0.0109 | 0.3789003 | 0.3784618 | NA | 0.1727240 | 33902 |
22 | 51216564 | rs9616970 | T | C | -0.0092 | 0.0109 | 0.3974001 | 0.3986489 | NA | 0.1563500 | 33902 |
22 | 51222100 | rs114553188 | G | T | -0.0308 | 0.0161 | 0.0559899 | 0.0557425 | NA | 0.0880591 | 33779 |
22 | 51223637 | rs375798137 | G | A | -0.0302 | 0.0162 | 0.0620098 | 0.0622940 | NA | 0.0788738 | 33779 |
1 693731 rs12238997 A G . PASS . ES:SE:LP:SS:ID -0.0013:0.0112:0.040577:32560:rs12238997
1 731718 rs58276399 T C . PASS . ES:SE:LP:SS:ID -0.0021:0.0109:0.0717578:32560:rs58276399
1 734349 rs141242758 T C . PASS . ES:SE:LP:SS:ID -0.0018:0.011:0.0590355:32560:rs141242758
1 736289 rs1254887344 T A . PASS . ES:SE:LP:SS:ID -0.0034:0.0108:0.124881:32848:rs1254887344
1 752566 rs3094315 G A . PASS . ES:SE:LP:SS:ID 0.0007:0.01:0.0257186:32520:rs3094315
1 753541 rs1388595942 G A . PASS . ES:SE:LP:SS:ID 0.0018:0.0106:0.0627329:33139:rs1388595942
1 766007 rs61768174 A C . PASS . ES:SE:LP:SS:ID 0.0027:0.0115:0.0894823:32560:rs61768174
1 768253 rs2977608 A C . PASS . ES:SE:LP:SS:ID 0.0021:0.0085:0.0921052:32848:rs2977608
1 768448 rs12562034 G A . PASS . ES:SE:LP:SS:ID -0.0095:0.0121:0.363312:32848:rs12562034
1 769223 rs60320384 C G . PASS . ES:SE:LP:SS:ID -0.001:0.0106:0.0334359:32879:rs60320384
1 771967 rs59066358 G A . PASS . ES:SE:LP:SS:ID -0.0007:0.0106:0.0230085:33139:rs59066358
1 777232 rs112618790 C T . PASS . ES:SE:LP:SS:ID -0.0101:0.0127:0.372737:32848:rs112618790
1 778745 rs1055606 A G . PASS . ES:SE:LP:SS:ID -0.0022:0.0107:0.078834:32879:rs1055606
1 779322 rs4040617 A G . PASS . ES:SE:LP:SS:ID -0.0025:0.0107:0.0893222:32879:rs4040617
1 781845 rs1391043716 A G . PASS . ES:SE:LP:SS:ID -0.0027:0.0116:0.0876716:32560:rs1391043716
1 782981 rs6594026 C T . PASS . ES:SE:LP:SS:ID -0.002:0.0106:0.0693566:32879:rs6594026
1 787606 rs3863622 G T . PASS . ES:SE:LP:SS:ID -0.0031:0.0107:0.11334:32879:rs3863622
1 790465 rs61768207 G A . PASS . ES:SE:LP:SS:ID -0.0032:0.0118:0.103529:32560:rs61768207
1 791191 rs111818025 G A . PASS . ES:SE:LP:SS:ID -0.0047:0.0107:0.179536:32879:rs111818025
1 791853 rs6684487 G A . PASS . ES:SE:LP:SS:ID -0.0064:0.0127:0.21254:32848:rs6684487
1 794332 rs12127425 G A . PASS . ES:SE:LP:SS:ID -0.0058:0.0138:0.169219:32594:rs12127425
1 795222 rs12131377 C G . PASS . ES:SE:LP:SS:ID -0.0082:0.0138:0.256412:32594:rs12131377
1 795988 rs59380221 C T . PASS . ES:SE:LP:SS:ID 0.0012:0.0109:0.040148:32560:rs59380221
1 796100 rs12132398 C T . PASS . ES:SE:LP:SS:ID -0.0093:0.0138:0.300596:32594:rs12132398
1 796375 rs1338880683 T C . PASS . ES:SE:LP:SS:ID -0.0054:0.011:0.204468:32820:rs1338880683
1 797281 rs1347695410 G C . PASS . ES:SE:LP:SS:ID -0.0096:0.0138:0.311758:32594:rs1347695410
1 797325 rs1338750774 T C . PASS . ES:SE:LP:SS:ID -0.0086:0.0138:0.272052:32594:rs1338750774
1 797440 rs58013264 T C . PASS . ES:SE:LP:SS:ID -0.0026:0.0091:0.111484:47114:rs58013264
1 798400 rs10900604 A G . PASS . ES:SE:LP:SS:ID -0.0041:0.0075:0.237246:47981:rs10900604
1 798801 rs12132517 G A . PASS . ES:SE:LP:SS:ID -0.0102:0.0138:0.336488:32594:rs12132517
1 798959 rs11240777 G A . PASS . ES:SE:LP:SS:ID -0.0032:0.0073:0.180061:49723:rs11240777
1 799499 rs147634896 T C . PASS . ES:SE:LP:SS:ID -0.0075:0.0138:0.233067:32594:rs147634896
1 801467 rs61768212 G C . PASS . ES:SE:LP:SS:ID -0.0024:0.0092:0.101714:46860:rs61768212
1 801661 rs12132974 C T . PASS . ES:SE:LP:SS:ID -0.0068:0.0139:0.204328:32594:rs12132974
1 801680 rs12134490 A C . PASS . ES:SE:LP:SS:ID -0.0073:0.0139:0.224026:32594:rs12134490
1 801858 rs17276806 C T . PASS . ES:SE:LP:SS:ID -0.0064:0.0139:0.189969:32594:rs17276806
1 802856 rs139867617 C T . PASS . ES:SE:LP:SS:ID -0.006:0.0139:0.177244:32594:rs139867617
1 804759 rs7526310 C T . PASS . ES:SE:LP:SS:ID -0.0016:0.0092:0.0645935:46860:rs7526310
1 808631 rs11240779 G A . PASS . ES:SE:LP:SS:ID 0.0023:0.0072:0.124476:47402:rs11240779
1 808928 rs1247187939 C T . PASS . ES:SE:LP:SS:ID 0.0026:0.0072:0.140922:47402:rs1247187939
1 809876 rs57181708 A G . PASS . ES:SE:LP:SS:ID -0.0131:0.0124:0.538952:32594:rs57181708
1 810286 rs28410559 G A . PASS . ES:SE:LP:SS:ID 0.0024:0.0111:0.0824945:32560:rs28410559
1 812743 rs6605064 C T . PASS . ES:SE:LP:SS:ID 0.0021:0.0111:0.0703257:32560:rs6605064
1 824398 rs7538305 A C . PASS . ES:SE:LP:SS:ID 0.0121:0.0108:0.579549:32594:rs7538305
1 830181 rs28444699 A G . PASS . ES:SE:LP:SS:ID -0.0046:0.0083:0.239804:32848:rs28444699
1 831489 rs4970385 C T . PASS . ES:SE:LP:SS:ID -0.0057:0.0082:0.31256:32848:rs4970385
1 831909 rs9697642 C T . PASS . ES:SE:LP:SS:ID -0.0061:0.0082:0.339324:32848:rs9697642
1 832066 rs9697380 G C . PASS . ES:SE:LP:SS:ID -0.0064:0.0082:0.360613:32848:rs9697380
1 832318 rs4500250 C A . PASS . ES:SE:LP:SS:ID -0.0062:0.0082:0.348819:32848:rs4500250
1 832398 rs4553118 T C . PASS . ES:SE:LP:SS:ID -0.0065:0.0085:0.354479:32848:rs4553118