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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/215cc62b-d828-4c02-808c-c32d25a65791/call-vcf/inputs/-261044443/upload.txt.gz --id ieu-b-4847 --json /data/cromwell-executions/qc/215cc62b-d828-4c02-808c-c32d25a65791/call-vcf/inputs/-261044443/ieu-b-4847_data.json --ref /data/cromwell-executions/qc/215cc62b-d828-4c02-808c-c32d25a65791/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/215cc62b-d828-4c02-808c-c32d25a65791/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-4847/ieu-b-4847.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/215cc62b-d828-4c02-808c-c32d25a65791/call-ldsc/inputs/-261044443/ieu-b-4847.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4847/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Wed Jan 5 14:35:53 2022
Reading summary statistics from /data/cromwell-executions/qc/215cc62b-d828-4c02-808c-c32d25a65791/call-ldsc/inputs/-261044443/ieu-b-4847.vcf.gz ...
Read summary statistics for 7907974 SNPs.
Dropped 38685 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, 1198584 SNPs remain.
After merging with regression SNP LD, 1198584 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0676 (0.0167)
Lambda GC: 1.0368
Mean Chi^2: 1.0455
Intercept: 1.0088 (0.0063)
Ratio: 0.1925 (0.1382)
Analysis finished at Wed Jan 5 14:37:36 2022
Total time elapsed: 1.0m:43.33s
{
"af_correlation": "NA",
"inflation_factor": 1.0354,
"mean_EFFECT": 0,
"n": 28130,
"n_snps": 7908033,
"n_clumped_hits": 0,
"n_p_sig": 0,
"n_mono": 0,
"n_ns": 285713,
"n_mac": 0,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 7908033,
"n_miss_AF_reference": 162519,
"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": 1198584,
"ldsc_nsnp_merge_regression_ld": 1198584,
"ldsc_observed_scale_h2_beta": 0.0676,
"ldsc_observed_scale_h2_se": 0.0167,
"ldsc_intercept_beta": 1.0088,
"ldsc_intercept_se": 0.0063,
"ldsc_lambda_gc": 1.0368,
"ldsc_mean_chisq": 1.0455,
"ldsc_ratio": 0.1934
}
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 | 14 | 0.9999982 | 3 | 58 | 0 | 7907906 | 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 | 6035 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | AF | 7908033 | 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 | 8.640807e+00 | 5.751369e+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 | 7.899674e+07 | 5.634699e+07 | 3.0200e+02 | 3.267372e+07 | 6.969050e+07 | 1.147522e+08 | 2.492223e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.110000e-05 | 1.905350e-02 | -1.8690e-01 | -9.200000e-03 | 0.000000e+00 | 9.200000e-03 | 1.970000e-01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.633000e-02 | 9.263900e-03 | 6.9000e-03 | 9.300000e-03 | 1.220000e-02 | 2.050000e-02 | 5.610000e-02 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.941799e-01 | 2.907767e-01 | 1.0000e-07 | 2.405000e-01 | 4.924997e-01 | 7.466997e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.941812e-01 | 2.907842e-01 | 2.0000e-07 | 2.403785e-01 | 4.925400e-01 | 7.467584e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF_reference | 162519 | 0.9794489 | NA | NA | NA | NA | NA | NA | NA | 2.652442e-01 | 2.521670e-01 | 1.9970e-04 | 5.770770e-02 | 1.799120e-01 | 4.141370e-01 | 1.000000e+00 | ▇▃▂▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.584257e+04 | 2.823634e+03 | 1.6201e+04 | 2.427100e+04 | 2.718600e+04 | 2.788100e+04 | 2.813000e+04 | ▁▁▁▁▇ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 797440 | rs58013264 | T | C | 0.0095 | 0.0129 | 0.4622001 | 0.4614666 | NA | 0.189497 | 25262 |
1 | 798400 | rs10900604 | A | G | 0.0019 | 0.0106 | 0.8596000 | 0.8577451 | NA | 0.410543 | 25485 |
1 | 798959 | rs11240777 | G | A | 0.0007 | 0.0106 | 0.9476001 | 0.9473478 | NA | 0.409944 | 25485 |
1 | 801467 | rs61768212 | G | C | 0.0087 | 0.0129 | 0.5010995 | 0.5000452 | NA | 0.193091 | 24997 |
1 | 804759 | rs7526310 | C | T | 0.0079 | 0.0129 | 0.5392995 | 0.5402711 | NA | 0.193890 | 24997 |
1 | 808223 | rs4951933 | G | C | -0.0061 | 0.0119 | 0.6070004 | 0.6082276 | NA | 0.452077 | 19046 |
1 | 808631 | rs11240779 | G | A | -0.0054 | 0.0102 | 0.5976006 | 0.5965198 | NA | 0.453474 | 25485 |
1 | 808928 | rs11240780 | C | T | -0.0051 | 0.0102 | 0.6133000 | 0.6170751 | NA | 0.452276 | 25485 |
1 | 845274 | rs112856858 | G | T | 0.0108 | 0.0126 | 0.3924000 | 0.3913659 | NA | 0.374002 | 19046 |
1 | 845635 | rs117086422 | C | T | 0.0127 | 0.0109 | 0.2447000 | 0.2439633 | NA | 0.158546 | 25485 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51181687 | rs9616955 | A | T | 0.0095 | 0.0210 | 0.6500998 | 0.6509946 | NA | 0.0485224 | 19046 |
22 | 51181759 | rs13056621 | A | G | -0.0060 | 0.0127 | 0.6356002 | 0.6366121 | NA | 0.6761180 | 26937 |
22 | 51182090 | rs28516879 | G | A | 0.0190 | 0.0165 | 0.2491002 | 0.2495204 | NA | 0.0467252 | 26672 |
22 | 51185848 | rs3865764 | G | A | 0.0172 | 0.0218 | 0.4282003 | 0.4301174 | NA | 0.9776360 | 24997 |
22 | 51186276 | rs8135434 | T | C | 0.0205 | 0.0217 | 0.3443000 | 0.3448118 | NA | 0.1076280 | 16408 |
22 | 51188319 | rs139620215 | T | C | 0.0112 | 0.0389 | 0.7727002 | 0.7734097 | NA | 0.0037939 | 24162 |
22 | 51197602 | rs187225588 | T | A | 0.0131 | 0.0238 | 0.5808005 | 0.5820312 | NA | 0.0175719 | 16408 |
22 | 51208568 | rs148425445 | G | T | 0.0158 | 0.0235 | 0.5011999 | 0.5013670 | NA | 0.1160140 | 16408 |
22 | 51216564 | rs9616970 | T | C | 0.0241 | 0.0162 | 0.1363000 | 0.1368421 | NA | 0.1563500 | 16201 |
22 | 51222100 | rs114553188 | G | T | 0.0221 | 0.0238 | 0.3529003 | 0.3531112 | NA | 0.0880591 | 16408 |
1 797440 rs58013264 T C . PASS . ES:SE:LP:SS:ID 0.0095:0.0129:0.33517:25262:rs58013264
1 798400 rs10900604 A G . PASS . ES:SE:LP:SS:ID 0.0019:0.0106:0.0657036:25485:rs10900604
1 798959 rs11240777 G A . PASS . ES:SE:LP:SS:ID 0.0007:0.0106:0.0233749:25485:rs11240777
1 801467 rs61768212 G C . PASS . ES:SE:LP:SS:ID 0.0087:0.0129:0.300076:24997:rs61768212
1 804759 rs7526310 C T . PASS . ES:SE:LP:SS:ID 0.0079:0.0129:0.26817:24997:rs7526310
1 808223 rs1557576983 G C . PASS . ES:SE:LP:SS:ID -0.0061:0.0119:0.216811:19046:rs1557576983
1 808631 rs11240779 G A . PASS . ES:SE:LP:SS:ID -0.0054:0.0102:0.223589:25485:rs11240779
1 808928 rs1247187939 C T . PASS . ES:SE:LP:SS:ID -0.0051:0.0102:0.212327:25485:rs1247187939
1 845274 rs1324283754 G T . PASS . ES:SE:LP:SS:ID 0.0108:0.0126:0.406271:19046:rs1324283754
1 845635 rs117086422 C T . PASS . ES:SE:LP:SS:ID 0.0127:0.0109:0.611366:25485:rs117086422
1 845938 rs57760052 G A . PASS . ES:SE:LP:SS:ID 0.0118:0.0108:0.559091:25485:rs57760052
1 846078 rs778265812 C T . PASS . ES:SE:LP:SS:ID 0.0109:0.0112:0.480435:25485:rs778265812
1 846398 rs58781670 G A . PASS . ES:SE:LP:SS:ID 0.0177:0.0109:0.975104:25485:rs58781670
1 846465 rs60454217 C T . PASS . ES:SE:LP:SS:ID 0.0037:0.0331:0.0400528:24162:rs60454217
1 846543 rs79396034 G T . PASS . ES:SE:LP:SS:ID -0.0157:0.0356:0.180061:20389:rs79396034
1 846808 rs4475691 C T . PASS . ES:SE:LP:SS:ID 0.0102:0.0111:0.445996:25485:rs4475691
1 846864 rs1269142199 G C . PASS . ES:SE:LP:SS:ID 0.0103:0.0112:0.445874:25485:rs1269142199
1 847228 rs3905286 C T . PASS . ES:SE:LP:SS:ID 0.0082:0.011:0.33885:25485:rs3905286
1 847491 rs1158719307 G A . PASS . ES:SE:LP:SS:ID 0.0091:0.0109:0.396531:25485:rs1158719307
1 848090 rs4246505 G A . PASS . ES:SE:LP:SS:ID 0.0093:0.0109:0.405829:25485:rs4246505
1 848445 rs1156895099 G A . PASS . ES:SE:LP:SS:ID 0.0082:0.0109:0.345631:25485:rs1156895099
1 848456 rs11507767 A G . PASS . ES:SE:LP:SS:ID 0.0083:0.0109:0.346787:25485:rs11507767
1 848738 rs3829741 C T . PASS . ES:SE:LP:SS:ID 0.0094:0.0109:0.406603:25485:rs3829741
1 850062 rs28723578 A T . PASS . ES:SE:LP:SS:ID 0.0087:0.0109:0.370387:25485:rs28723578
1 850123 rs28622257 C T . PASS . ES:SE:LP:SS:ID 0.0087:0.0109:0.372122:25485:rs28622257
1 851190 rs28609852 G A . PASS . ES:SE:LP:SS:ID 0.0084:0.0109:0.358229:25485:rs28609852
1 851204 rs28552953 G C . PASS . ES:SE:LP:SS:ID 0.0085:0.0108:0.369369:25485:rs28552953
1 852664 rs28605311 C T . PASS . ES:SE:LP:SS:ID 0.0082:0.011:0.34218:25485:rs28605311
1 852758 rs4970462 G C . PASS . ES:SE:LP:SS:ID 0.0083:0.0113:0.333576:24650:rs4970462
1 853239 rs4970380 A G . PASS . ES:SE:LP:SS:ID 0.0087:0.011:0.367644:25485:rs4970380
1 853805 rs3748591 C T . PASS . ES:SE:LP:SS:ID 0.0112:0.0294:0.152366:24162:rs3748591
1 854250 rs7537756 A G . PASS . ES:SE:LP:SS:ID 0.0082:0.011:0.341416:25485:rs7537756
1 854429 rs72902552 G A . PASS . ES:SE:LP:SS:ID 0.0123:0.0294:0.170761:24162:rs72902552
1 856436 rs34105146 TG T . PASS . ES:SE:LP:SS:ID 0.0017:0.013:0.0489054:19046:rs34105146
1 856476 rs4040605 A G . PASS . ES:SE:LP:SS:ID 0.0065:0.0092:0.3213:25485:rs4040605
1 857177 rs386627408 T C . PASS . ES:SE:LP:SS:ID 0.0036:0.029:0.0448898:24162:rs386627408
1 858040 rs4970460 C A . PASS . ES:SE:LP:SS:ID 0.0065:0.0108:0.263763:25485:rs4970460
1 858051 rs4970459 C T . PASS . ES:SE:LP:SS:ID 0.007:0.0108:0.284749:25485:rs4970459
1 858801 rs7418179 A G . PASS . ES:SE:LP:SS:ID -0.0091:0.0107:0.404614:24650:rs7418179
1 859404 rs71509444 C G . PASS . ES:SE:LP:SS:ID -0.0064:0.0326:0.0730919:19046:rs71509444
1 859685 rs111572704 G A . PASS . ES:SE:LP:SS:ID -0.0003:0.0127:0.00930604:19046:rs111572704
1 859690 rs71509445 C G . PASS . ES:SE:LP:SS:ID -0.0031:0.035:0.0321713:19046:rs71509445
1 859701 rs71509446 C G . PASS . ES:SE:LP:SS:ID -0.0031:0.035:0.0321713:19046:rs71509446
1 859913 rs1187056171 A G . PASS . ES:SE:LP:SS:ID -0.0091:0.0319:0.110698:24162:rs1187056171
1 860416 rs61464428 G A . PASS . ES:SE:LP:SS:ID -0.0085:0.0104:0.380802:25485:rs61464428
1 860461 rs57465118 G A . PASS . ES:SE:LP:SS:ID -0.0096:0.0284:0.134422:24162:rs57465118
1 860521 rs57924093 C A . PASS . ES:SE:LP:SS:ID -0.0096:0.0284:0.134422:24162:rs57924093
1 860688 rs60837925 G A . PASS . ES:SE:LP:SS:ID -0.0084:0.0104:0.378512:25485:rs60837925
1 860854 rs57816555 T C . PASS . ES:SE:LP:SS:ID 0.0111:0.0376:0.114582:19046:rs57816555
1 861008 rs28521172 G C . PASS . ES:SE:LP:SS:ID -0.01:0.0284:0.139303:24162:rs28521172