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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/746747eb-99a7-44b0-94d4-cafd3c362001/call-ldsc/inputs/-261043605/ieu-b-4908.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4908/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Thu Mar 3 20:48:37 2022
Reading summary statistics from /data/cromwell-executions/qc/746747eb-99a7-44b0-94d4-cafd3c362001/call-ldsc/inputs/-261043605/ieu-b-4908.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 Thu Mar 3 20:49:24 2022
Total time elapsed: 47.53s
{
"af_correlation": 0.5875,
"inflation_factor": 0.999,
"mean_EFFECT": 0.0023,
"n": "-Inf",
"n_snps": 7246993,
"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": 0,
"n_miss_AF_reference": 75734,
"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 | TRUE |
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 | 132 | 0.9999818 | 3 | 58 | 0 | 7242925 | 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 | 7246993 | 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 | 8.656778e+00 | 5.769714e+00 | 1.0000000 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 7.891601e+07 | 5.635140e+07 | 828.0000000 | 3.250790e+07 | 6.937929e+07 | 1.147037e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.321100e-03 | 1.564145e+00 | -917.3020000 | -9.883920e-02 | 3.780000e-05 | 9.934140e-02 | 1.058620e+03 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.960959e-01 | 2.110647e+00 | 0.0775370 | 9.779510e-02 | 1.357650e-01 | 2.391900e-01 | 1.056850e+03 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.996707e-01 | 2.892194e-01 | 0.0000004 | 2.488301e-01 | 5.002165e-01 | 7.501947e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.990752e-01 | 2.895766e-01 | 0.0000002 | 2.477964e-01 | 4.996316e-01 | 7.499458e-01 | 9.999997e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.683334e-01 | 1.474396e-01 | 0.0096754 | 3.631400e-02 | 1.193600e-01 | 2.811500e-01 | 5.000000e-01 | ▇▃▂▂▂ |
numeric | AF_reference | 75734 | 0.9895496 | NA | NA | NA | NA | NA | NA | NA | 2.455154e-01 | 2.513944e-01 | 0.0000000 | 4.053510e-02 | 1.529550e-01 | 3.829870e-01 | 1.000000e+00 | ▇▃▂▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | 0.114378 | 0.456916 | 0.8025271 | 0.8023352 | 0.359860 | 0.7821490 | NA |
1 | 54676 | rs2462492 | C | T | -0.534404 | 0.420910 | 0.2053180 | 0.2042130 | 0.388830 | NA | NA |
1 | 86028 | rs114608975 | T | C | 1.318850 | 0.808291 | 0.1039319 | 0.1027527 | 0.098238 | 0.0277556 | NA |
1 | 91536 | rs6702460 | G | T | 0.209953 | 0.421189 | 0.6185574 | 0.6181479 | 0.453670 | 0.4207270 | NA |
1 | 234313 | rs8179466 | C | T | -0.242411 | 0.687578 | 0.7246979 | 0.7244200 | 0.079244 | NA | NA |
1 | 534192 | rs6680723 | C | T | -0.783669 | 0.477199 | 0.1017199 | 0.1005430 | 0.240840 | NA | NA |
1 | 546697 | rs12025928 | A | G | -0.461036 | 0.484088 | 0.3417661 | 0.3409040 | 0.086871 | NA | NA |
1 | 568800 | rs375217967 | G | A | 1.073420 | 0.947988 | 0.2585187 | 0.2575025 | 0.016076 | 0.0778754 | NA |
1 | 569004 | rs9285835 | T | C | -5.293950 | 2.553610 | 0.0391201 | 0.0381607 | 0.012532 | NA | NA |
1 | 569624 | rs6594035 | T | C | 0.327027 | 2.586430 | 0.8994789 | 0.8993840 | 0.011422 | NA | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219387 | rs9616832 | T | C | 0.0341765 | 0.195083 | 0.8610639 | 0.8609307 | 0.073955 | 0.0654952 | NA |
22 | 51219704 | rs147475742 | G | A | -0.0733929 | 0.275757 | 0.7903273 | 0.7901232 | 0.041917 | 0.0473243 | NA |
22 | 51220517 | rs9616980 | C | G | 0.3381740 | 0.566017 | 0.5507050 | 0.5501986 | 0.011741 | 0.0027955 | NA |
22 | 51221190 | rs369304721 | G | A | -0.0286750 | 0.262365 | 0.9130509 | 0.9129691 | 0.049718 | NA | NA |
22 | 51221731 | rs115055839 | T | C | 0.0338984 | 0.195402 | 0.8624051 | 0.8622739 | 0.073062 | 0.0625000 | NA |
22 | 51222100 | rs114553188 | G | T | -0.3571000 | 0.216765 | 0.1006501 | 0.0994746 | 0.053551 | 0.0880591 | NA |
22 | 51223637 | rs375798137 | G | A | -0.3581860 | 0.217063 | 0.1000889 | 0.0989127 | 0.053086 | 0.0788738 | NA |
22 | 51229805 | rs9616985 | T | C | 0.0338253 | 0.195734 | 0.8629301 | 0.8627987 | 0.073123 | 0.0730831 | NA |
22 | 51232488 | rs376461333 | A | G | -0.5943610 | 0.423405 | 0.1615511 | 0.1603889 | 0.020104 | NA | NA |
22 | 51237063 | rs3896457 | T | C | 0.1417570 | 0.106878 | 0.1858570 | 0.1847258 | 0.294910 | 0.2050720 | NA |
1 49298 rs10399793 T C . PASS AF=0.35986 ES:SE:LP:AF:ID 0.114378:0.456916:0.0955403:0.35986:rs10399793
1 54676 rs2462492 C T . PASS AF=0.38883 ES:SE:LP:AF:ID -0.534404:0.42091:0.687573:0.38883:rs2462492
1 86028 rs114608975 T C . PASS AF=0.098238 ES:SE:LP:AF:ID 1.31885:0.808291:0.983251:0.098238:rs114608975
1 91536 rs1251109649 G T . PASS AF=0.45367 ES:SE:LP:AF:ID 0.209953:0.421189:0.20862:0.45367:rs1251109649
1 234313 rs8179466 C T . PASS AF=0.079244 ES:SE:LP:AF:ID -0.242411:0.687578:0.139843:0.079244:rs8179466
1 534192 rs6680723 C T . PASS AF=0.24084 ES:SE:LP:AF:ID -0.783669:0.477199:0.992594:0.24084:rs6680723
1 546697 rs12025928 A G . PASS AF=0.086871 ES:SE:LP:AF:ID -0.461036:0.484088:0.466271:0.086871:rs12025928
1 568800 rs375217967 G A . PASS AF=0.016076 ES:SE:LP:AF:ID 1.07342:0.947988:0.587508:0.016076:rs375217967
1 569004 rs9285835 T C . PASS AF=0.012532 ES:SE:LP:AF:ID -5.29395:2.55361:1.4076:0.012532:rs9285835
1 569624 rs6594035 T C . PASS AF=0.011422 ES:SE:LP:AF:ID 0.327027:2.58643:0.046009:0.011422:rs6594035
1 693731 rs12238997 A G . PASS AF=0.12394 ES:SE:LP:AF:ID 0.766406:0.407467:1.21415:0.12394:rs12238997
1 705882 rs72631875 G A . PASS AF=0.071517 ES:SE:LP:AF:ID -0.404071:0.54409:0.338809:0.071517:rs72631875
1 706368 rs963699400 A G . PASS AF=0.48937 ES:SE:LP:AF:ID -0.14414:0.228776:0.276379:0.48937:rs963699400
1 714596 rs149887893 T C . PASS AF=0.036483 ES:SE:LP:AF:ID 1.20858:1.35812:0.426751:0.036483:rs149887893
1 715265 rs12184267 C T . PASS AF=0.040536 ES:SE:LP:AF:ID 0.682336:1.37603:0.207334:0.040536:rs12184267
1 715367 rs12184277 A G . PASS AF=0.040763 ES:SE:LP:AF:ID 0.722097:1.37614:0.221698:0.040763:rs12184277
1 717485 rs12184279 C A . PASS AF=0.040352 ES:SE:LP:AF:ID 0.762118:1.38924:0.233775:0.040352:rs12184279
1 717587 rs144155419 G A . PASS AF=0.016514 ES:SE:LP:AF:ID -0.0298361:1.14435:0.00912017:0.016514:rs144155419
1 720381 rs116801199 G T . PASS AF=0.040909 ES:SE:LP:AF:ID 0.638612:1.36781:0.193167:0.040909:rs116801199
1 721290 rs12565286 G C . PASS AF=0.041095 ES:SE:LP:AF:ID 0.480538:1.36697:0.139384:0.041095:rs12565286
1 722670 rs116030099 T C . PASS AF=0.099265 ES:SE:LP:AF:ID 0.247439:0.444446:0.237941:0.099265:rs116030099
1 723891 rs2977670 G C . PASS AF=0.047367 ES:SE:LP:AF:ID 0.284077:0.860915:0.129783:0.047367:rs2977670
1 724849 rs12126395 C A . PASS AF=0.030038 ES:SE:LP:AF:ID 4.68756:1.50377:2.69354:0.030038:rs12126395
1 725060 rs1445661281 A T . PASS AF=0.052781 ES:SE:LP:AF:ID -1.23993:0.680194:1.15841:0.052781:rs1445661281
1 726794 rs28454925 C G . PASS AF=0.040513 ES:SE:LP:AF:ID 0.577922:1.36935:0.171769:0.040513:rs28454925
1 729632 rs116720794 C T . PASS AF=0.040678 ES:SE:LP:AF:ID 0.753265:1.37795:0.232791:0.040678:rs116720794
1 729679 rs4951859 C G . PASS AF=0.16855 ES:SE:LP:AF:ID -0.551686:0.367142:0.872536:0.16855:rs4951859
1 730087 rs148120343 T C . PASS AF=0.053483 ES:SE:LP:AF:ID 0.728625:0.647805:0.582195:0.053483:rs148120343
1 731453 rs186002080 G A . PASS AF=0.015304 ES:SE:LP:AF:ID -0.832867:0.932818:0.428593:0.015304:rs186002080
1 731718 rs58276399 T C . PASS AF=0.13048 ES:SE:LP:AF:ID 0.66937:0.385967:1.07559:0.13048:rs58276399
1 732989 rs369030935 C T . PASS AF=0.021775 ES:SE:LP:AF:ID -0.502739:0.635447:0.366982:0.021775:rs369030935
1 734349 rs141242758 T C . PASS AF=0.12935 ES:SE:LP:AF:ID 0.680532:0.385286:1.1052:0.12935:rs141242758
1 736289 rs1254887344 T A . PASS AF=0.13925 ES:SE:LP:AF:ID 0.881096:0.407405:1.50235:0.13925:rs1254887344
1 752478 rs146277091 G A . PASS AF=0.040427 ES:SE:LP:AF:ID 1.08435:1.3978:0.357951:0.040427:rs146277091
1 752566 rs3094315 G A . PASS AF=0.17073 ES:SE:LP:AF:ID -0.89555:0.36026:1.86849:0.17073:rs3094315
1 752721 rs3131972 A G . PASS AF=0.17249 ES:SE:LP:AF:ID -0.815472:0.353211:1.6631:0.17249:rs3131972
1 753405 rs3115860 C A . PASS AF=0.13929 ES:SE:LP:AF:ID -0.823527:0.355497:1.67192:0.13929:rs3115860
1 753541 rs1388595942 G A . PASS AF=0.13958 ES:SE:LP:AF:ID 0.761604:0.352902:1.49743:0.13958:rs1388595942
1 754063 rs12184312 G T . PASS AF=0.040063 ES:SE:LP:AF:ID 0.730975:1.41384:0.217833:0.040063:rs12184312
1 754105 rs12184325 C T . PASS AF=0.040029 ES:SE:LP:AF:ID 0.661912:1.41704:0.193276:0.040029:rs12184325
1 754182 rs3131969 A G . PASS AF=0.14121 ES:SE:LP:AF:ID -0.754688:0.349152:1.50105:0.14121:rs3131969
1 754192 rs3131968 A G . PASS AF=0.14109 ES:SE:LP:AF:ID -0.755349:0.349146:1.50312:0.14109:rs3131968
1 754211 rs12184313 G A . PASS AF=0.040203 ES:SE:LP:AF:ID 0.713266:1.41807:0.21085:0.040203:rs12184313
1 754334 rs3131967 T C . PASS AF=0.14107 ES:SE:LP:AF:ID -0.758035:0.349232:1.51083:0.14107:rs3131967
1 754503 rs3115859 G A . PASS AF=0.17227 ES:SE:LP:AF:ID -0.821862:0.353567:1.6809:0.17227:rs3115859
1 754629 rs10454459 A G . PASS AF=0.040591 ES:SE:LP:AF:ID 0.65969:1.38102:0.198413:0.040591:rs10454459
1 754964 rs3131966 C T . PASS AF=0.1717 ES:SE:LP:AF:ID -0.81688:0.353231:1.66745:0.1717:rs3131966
1 755240 rs181660517 T G . PASS AF=0.011824 ES:SE:LP:AF:ID -0.116548:1.41119:0.0295411:0.011824:rs181660517
1 755775 rs3131965 A G . PASS AF=0.1692 ES:SE:LP:AF:ID -0.750209:0.359804:1.42005:0.1692:rs3131965
1 755890 rs1280367067 A T . PASS AF=0.13948 ES:SE:LP:AF:ID -0.816024:0.354936:1.65222:0.13948:rs1280367067