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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/4ef9477d-b87a-4522-9af1-7aec3e1d35ae/call-ldsc/inputs/-261045349/ieu-b-4760.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4760/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Tue Aug 24 16:59:52 2021
Reading summary statistics from /data/cromwell-executions/qc/4ef9477d-b87a-4522-9af1-7aec3e1d35ae/call-ldsc/inputs/-261045349/ieu-b-4760.vcf.gz ...
Read summary statistics for 0 SNPs.
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.
Traceback (most recent call last):
File "./ldsc/ldsc.py", line 647, in <module>
sumstats.estimate_h2(args, log)
File "/ldsc/ldscore/sumstats.py", line 330, in estimate_h2
args, log, args.h2)
File "/ldsc/ldscore/sumstats.py", line 252, in _read_ld_sumstats
sumstats = _merge_and_log(ref_ld, sumstats, 'reference panel LD', log)
File "/ldsc/ldscore/sumstats.py", line 238, in _merge_and_log
raise ValueError(msg.format(N=len(sumstats), F=noun))
ValueError: After merging with reference panel LD, 0 SNPs remain.
Analysis finished at Tue Aug 24 17:00:44 2021
Total time elapsed: 52.35s
{
"af_correlation": 0.9494,
"inflation_factor": 1.1919,
"mean_EFFECT": 6.1286e-06,
"n": "-Inf",
"n_snps": 9631490,
"n_clumped_hits": 9,
"n_p_sig": 939,
"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": 0,
"n_miss_AF_reference": 142774,
"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": 0,
"ldsc_nsnp_merge_regression_ld": "NA",
"ldsc_observed_scale_h2_beta": "NA",
"ldsc_observed_scale_h2_se": "NA",
"ldsc_intercept_beta": "NA",
"ldsc_intercept_se": "NA",
"ldsc_lambda_gc": "NA",
"ldsc_mean_chisq": "NA",
"ldsc_ratio": "NA"
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | FALSE |
n | TRUE |
is_snpid_non_unique | TRUE |
mean_EFFECT_nonfinite | FALSE |
mean_EFFECT_05 | FALSE |
mean_EFFECT_01 | FALSE |
mean_chisq | NA |
n_p_sig | FALSE |
miss_EFFECT | FALSE |
miss_SE | FALSE |
miss_PVAL | FALSE |
ldsc_ratio | NA |
ldsc_intercept_beta | NA |
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 | 65 | 0.9999933 | 3 | 58 | 0 | 9631299 | 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 | N | 9631490 | 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 | 8.625340e+00 | 5.751054e+00 | 1.0000 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▃▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 7.884816e+07 | 5.629880e+07 | 828.0000 | 3.256524e+07 | 6.944762e+07 | 1.145820e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 6.100000e-06 | 9.644700e-03 | -0.1861 | -3.100000e-03 | 0.000000e+00 | 3.100000e-03 | 4.596000e-01 | ▁▇▁▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 6.621900e-03 | 6.571900e-03 | 0.0019 | 2.400000e-03 | 3.900000e-03 | 8.700000e-03 | 1.674000e-01 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.712439e-01 | 2.964466e-01 | 0.0000 | 2.078002e-01 | 4.615003e-01 | 7.280999e-01 | 1.000000e+00 | ▇▆▆▆▆ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.710952e-01 | 2.965843e-01 | 0.0000 | 2.079367e-01 | 4.604566e-01 | 7.279708e-01 | 1.000000e+00 | ▇▆▆▆▆ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.070865e-01 | 2.570060e-01 | 0.0014 | 1.470000e-02 | 8.310000e-02 | 3.234000e-01 | 9.986000e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 142774 | 0.9851763 | NA | NA | NA | NA | NA | NA | NA | 2.093574e-01 | 2.486414e-01 | 0.0000 | 1.277960e-02 | 1.036340e-01 | 3.254790e-01 | 1.000000e+00 | ▇▂▁▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | 0.0046 | 0.0036 | 0.1935998 | 0.2013278 | 0.6239 | 0.7821490 | NA |
1 | 54676 | rs2462492 | C | T | 0.0052 | 0.0035 | 0.1419999 | 0.1373547 | 0.4002 | NA | NA |
1 | 86028 | rs114608975 | T | C | -0.0008 | 0.0056 | 0.8913999 | 0.8864030 | 0.1036 | 0.0277556 | NA |
1 | 91536 | rs6702460 | G | T | 0.0012 | 0.0035 | 0.7380997 | 0.7317059 | 0.4568 | 0.4207270 | NA |
1 | 234313 | rs8179466 | C | T | -0.0135 | 0.0069 | 0.0492006 | 0.0504037 | 0.0745 | NA | NA |
1 | 534192 | rs6680723 | C | T | -0.0036 | 0.0040 | 0.3602002 | 0.3681203 | 0.2409 | NA | NA |
1 | 546697 | rs12025928 | A | G | -0.0005 | 0.0050 | 0.9163000 | 0.9203443 | 0.9135 | NA | NA |
1 | 693731 | rs12238997 | A | G | 0.0000 | 0.0033 | 0.9930000 | 1.0000000 | 0.1162 | 0.1417730 | NA |
1 | 705882 | rs72631875 | G | A | -0.0114 | 0.0049 | 0.0195799 | 0.0199903 | 0.0673 | 0.0315495 | NA |
1 | 706368 | rs55727773 | A | G | -0.0002 | 0.0025 | 0.9462999 | 0.9362373 | 0.5158 | 0.2751600 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219704 | rs147475742 | G | A | -0.0076 | 0.0052 | 0.1435000 | 0.1438677 | 0.0420 | 0.0473243 | NA |
22 | 51219766 | rs182321900 | C | T | -0.0113 | 0.0240 | 0.6381004 | 0.6377598 | 0.0020 | NA | NA |
22 | 51220146 | rs868950473 | C | T | -0.0107 | 0.0238 | 0.6529005 | 0.6530134 | 0.0020 | NA | NA |
22 | 51221190 | rs369304721 | G | A | -0.0053 | 0.0052 | 0.3021997 | 0.3080934 | 0.0498 | NA | NA |
22 | 51221731 | rs115055839 | T | C | -0.0050 | 0.0039 | 0.1933998 | 0.1998247 | 0.0733 | 0.0625000 | NA |
22 | 51222100 | rs114553188 | G | T | 0.0007 | 0.0046 | 0.8695000 | 0.8790498 | 0.0544 | 0.0880591 | NA |
22 | 51223637 | rs375798137 | G | A | 0.0005 | 0.0046 | 0.9117001 | 0.9134439 | 0.0540 | 0.0788738 | NA |
22 | 51229805 | rs9616985 | T | C | -0.0049 | 0.0039 | 0.2025000 | 0.2089673 | 0.0731 | 0.0730831 | NA |
22 | 51232488 | rs376461333 | A | G | 0.0098 | 0.0091 | 0.2844003 | 0.2815146 | 0.0200 | NA | NA |
22 | 51237063 | rs3896457 | T | C | 0.0022 | 0.0024 | 0.3529003 | 0.3593173 | 0.2980 | 0.2050720 | NA |
1 49298 rs10399793 T C . PASS AF=0.6239 ES:SE:LP:AF:ID 0.0046:0.0036:0.713095:0.6239:rs10399793
1 54676 rs2462492 C T . PASS AF=0.4002 ES:SE:LP:AF:ID 0.0052:0.0035:0.847712:0.4002:rs2462492
1 86028 rs114608975 T C . PASS AF=0.1036 ES:SE:LP:AF:ID -0.0008:0.0056:0.0499274:0.1036:rs114608975
1 91536 rs1251109649 G T . PASS AF=0.4568 ES:SE:LP:AF:ID 0.0012:0.0035:0.131885:0.4568:rs1251109649
1 234313 rs8179466 C T . PASS AF=0.0745 ES:SE:LP:AF:ID -0.0135:0.0069:1.30803:0.0745:rs8179466
1 534192 rs6680723 C T . PASS AF=0.2409 ES:SE:LP:AF:ID -0.0036:0.004:0.443456:0.2409:rs6680723
1 546697 rs12025928 A G . PASS AF=0.9135 ES:SE:LP:AF:ID -0.0005:0.005:0.0379623:0.9135:rs12025928
1 693731 rs12238997 A G . PASS AF=0.1162 ES:SE:LP:AF:ID -0:0.0033:0.00305075:0.1162:rs12238997
1 705882 rs72631875 G A . PASS AF=0.0673 ES:SE:LP:AF:ID -0.0114:0.0049:1.70819:0.0673:rs72631875
1 706368 rs963699400 A G . PASS AF=0.5158 ES:SE:LP:AF:ID -0.0002:0.0025:0.0239712:0.5158:rs963699400
1 714596 rs149887893 T C . PASS AF=0.033 ES:SE:LP:AF:ID 0.0056:0.0062:0.437707:0.033:rs149887893
1 715265 rs12184267 C T . PASS AF=0.0367 ES:SE:LP:AF:ID 0.0062:0.0056:0.568958:0.0367:rs12184267
1 715367 rs12184277 A G . PASS AF=0.0368 ES:SE:LP:AF:ID 0.0055:0.0056:0.480829:0.0368:rs12184277
1 717485 rs12184279 C A . PASS AF=0.0365 ES:SE:LP:AF:ID 0.0056:0.0057:0.487182:0.0365:rs12184279
1 717587 rs144155419 G A . PASS AF=0.0164 ES:SE:LP:AF:ID -0.0031:0.0087:0.142668:0.0164:rs144155419
1 720381 rs116801199 G T . PASS AF=0.037 ES:SE:LP:AF:ID 0.006:0.0056:0.54333:0.037:rs116801199
1 721290 rs12565286 G C . PASS AF=0.0371 ES:SE:LP:AF:ID 0.0054:0.0056:0.4786:0.0371:rs12565286
1 722670 rs116030099 T C . PASS AF=0.1013 ES:SE:LP:AF:ID -0.0014:0.0041:0.131062:0.1013:rs116030099
1 723891 rs2977670 G C . PASS AF=0.959 ES:SE:LP:AF:ID -0.0072:0.0054:0.748849:0.959:rs2977670
1 724849 rs12126395 C A . PASS AF=0.0315 ES:SE:LP:AF:ID 0.0175:0.0098:1.13042:0.0315:rs12126395
1 725060 rs1445661281 A T . PASS AF=0.0532 ES:SE:LP:AF:ID 0.0081:0.0078:0.523024:0.0532:rs1445661281
1 726794 rs28454925 C G . PASS AF=0.0366 ES:SE:LP:AF:ID 0.0055:0.0056:0.487983:0.0366:rs28454925
1 729632 rs116720794 C T . PASS AF=0.0369 ES:SE:LP:AF:ID 0.0049:0.0056:0.425853:0.0369:rs116720794
1 729679 rs4951859 C G . PASS AF=0.8433 ES:SE:LP:AF:ID -0.0023:0.0029:0.363713:0.8433:rs4951859
1 730087 rs148120343 T C . PASS AF=0.0559 ES:SE:LP:AF:ID -0.0014:0.0047:0.11685:0.0559:rs148120343
1 731718 rs58276399 T C . PASS AF=0.1222 ES:SE:LP:AF:ID 0.0007:0.0032:0.0781055:0.1222:rs58276399
1 732989 rs369030935 C T . PASS AF=0.0258 ES:SE:LP:AF:ID 0.0063:0.0078:0.378512:0.0258:rs369030935
1 734349 rs141242758 T C . PASS AF=0.1215 ES:SE:LP:AF:ID 0.0002:0.0032:0.0258108:0.1215:rs141242758
1 736289 rs1254887344 T A . PASS AF=0.1323 ES:SE:LP:AF:ID 0.0019:0.0031:0.268653:0.1323:rs1254887344
1 736689 rs181876450 T C . PASS AF=0.0111 ES:SE:LP:AF:ID 0.0125:0.0113:0.56671:0.0111:rs181876450
1 740284 rs61770167 C T . PASS AF=0.0057 ES:SE:LP:AF:ID 0.0203:0.0147:0.778064:0.0057:rs61770167
1 742813 rs112573343 C T . PASS AF=0.0023 ES:SE:LP:AF:ID 0.0387:0.0245:0.940437:0.0023:rs112573343
1 752478 rs146277091 G A . PASS AF=0.0369 ES:SE:LP:AF:ID 0.0051:0.0055:0.449283:0.0369:rs146277091
1 752566 rs3094315 G A . PASS AF=0.839 ES:SE:LP:AF:ID -0.0016:0.0028:0.2423:0.839:rs3094315
1 752721 rs3131972 A G . PASS AF=0.8386 ES:SE:LP:AF:ID -0.0016:0.0028:0.253989:0.8386:rs3131972
1 753405 rs3115860 C A . PASS AF=0.8699 ES:SE:LP:AF:ID -0.0007:0.003:0.0914078:0.8699:rs3115860
1 753541 rs1388595942 G A . PASS AF=0.1298 ES:SE:LP:AF:ID 0.0002:0.003:0.0283068:0.1298:rs1388595942
1 754063 rs12184312 G T . PASS AF=0.0374 ES:SE:LP:AF:ID 0.0051:0.0054:0.460422:0.0374:rs12184312
1 754105 rs12184325 C T . PASS AF=0.0376 ES:SE:LP:AF:ID 0.0049:0.0054:0.443698:0.0376:rs12184325
1 754182 rs3131969 A G . PASS AF=0.8692 ES:SE:LP:AF:ID -0.0008:0.003:0.101824:0.8692:rs3131969
1 754192 rs3131968 A G . PASS AF=0.8693 ES:SE:LP:AF:ID -0.0008:0.003:0.102428:0.8693:rs3131968
1 754211 rs12184313 G A . PASS AF=0.0376 ES:SE:LP:AF:ID 0.0048:0.0054:0.43086:0.0376:rs12184313
1 754334 rs3131967 T C . PASS AF=0.8692 ES:SE:LP:AF:ID -0.0008:0.003:0.0991415:0.8692:rs3131967
1 754433 rs150578204 G A . PASS AF=0.0051 ES:SE:LP:AF:ID -0.0159:0.0153:0.523458:0.0051:rs150578204
1 754458 rs1242318281 G T . PASS AF=0.0051 ES:SE:LP:AF:ID -0.0159:0.0154:0.523458:0.0051:rs1242318281
1 754503 rs3115859 G A . PASS AF=0.8381 ES:SE:LP:AF:ID -0.0018:0.0028:0.280255:0.8381:rs3115859
1 754629 rs10454459 A G . PASS AF=0.0376 ES:SE:LP:AF:ID 0.0048:0.0054:0.431095:0.0376:rs10454459
1 754964 rs3131966 C T . PASS AF=0.8387 ES:SE:LP:AF:ID -0.0019:0.0028:0.29465:0.8387:rs3131966
1 755240 rs181660517 T G . PASS AF=0.0137 ES:SE:LP:AF:ID -0.0064:0.0098:0.291154:0.0137:rs181660517
1 755435 rs1557550616 T G . PASS AF=0.0055 ES:SE:LP:AF:ID 0.018:0.015:0.633577:0.0055:rs1557550616