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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/0abdc8a1-0783-4d56-ac67-aae76a6dd892/call-ldsc/inputs/-261044503/ieu-b-4829.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4829/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Wed Jan 5 09:23:24 2022
Reading summary statistics from /data/cromwell-executions/qc/0abdc8a1-0783-4d56-ac67-aae76a6dd892/call-ldsc/inputs/-261044503/ieu-b-4829.vcf.gz ...
Read summary statistics for 7908896 SNPs.
Dropped 38670 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, 1197303 SNPs remain.
After merging with regression SNP LD, 1197303 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0713 (0.0145)
Lambda GC: 0.977
Mean Chi^2: 1.0529
Intercept: 1.0083 (0.0063)
Ratio: 0.1569 (0.1184)
Analysis finished at Wed Jan 5 09:25:11 2022
Total time elapsed: 1.0m:47.13s
{
"af_correlation": "NA",
"inflation_factor": 1.0576,
"mean_EFFECT": -2.0673e-06,
"n": 31740,
"n_snps": 7908954,
"n_clumped_hits": 2,
"n_p_sig": 7,
"n_mono": 0,
"n_ns": 285832,
"n_mac": 0,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 7908954,
"n_miss_AF_reference": 161404,
"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": 1197303,
"ldsc_nsnp_merge_regression_ld": 1197303,
"ldsc_observed_scale_h2_beta": 0.0713,
"ldsc_observed_scale_h2_se": 0.0145,
"ldsc_intercept_beta": 1.0083,
"ldsc_intercept_se": 0.0063,
"ldsc_lambda_gc": 0.977,
"ldsc_mean_chisq": 1.0529,
"ldsc_ratio": 0.1569
}
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 | 7908828 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 43 | 0 | 16662 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 44 | 0 | 6028 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | AF | 7908954 | 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 | 8.639183e+00 | 5.750530e+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 | 7.899430e+07 | 5.634273e+07 | 3.0200e+02 | 3.267020e+07 | 6.968960e+07 | 1.147462e+08 | 2.492223e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -2.100000e-06 | 1.037100e-03 | -1.0000e-02 | -5.000000e-04 | 0.000000e+00 | 5.000000e-04 | 1.030000e-02 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 8.984000e-04 | 4.805000e-04 | 4.0000e-04 | 5.000000e-04 | 7.000000e-04 | 1.100000e-03 | 2.900000e-03 | ▇▂▂▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.912438e-01 | 2.906513e-01 | 0.0000e+00 | 2.376999e-01 | 4.879002e-01 | 7.426993e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.932680e-01 | 2.925548e-01 | 0.0000e+00 | 2.301393e-01 | 5.049851e-01 | 7.388827e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF_reference | 161404 | 0.9795922 | NA | NA | NA | NA | NA | NA | NA | 2.651678e-01 | 2.522192e-01 | 1.9970e-04 | 5.770770e-02 | 1.797120e-01 | 4.141370e-01 | 1.000000e+00 | ▇▃▂▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 3.053130e+04 | 1.635262e+03 | 1.7761e+04 | 2.982200e+04 | 3.092700e+04 | 3.174000e+04 | 3.174000e+04 | ▁▁▁▁▇ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 797440 | rs58013264 | T | C | 1e-04 | 7e-04 | 0.9254000 | 0.8864030 | NA | 0.189497 | 30271 |
1 | 798400 | rs10900604 | A | G | 2e-04 | 6e-04 | 0.7235008 | 0.7388827 | NA | 0.410543 | 30827 |
1 | 798959 | rs11240777 | G | A | 2e-04 | 6e-04 | 0.7327992 | 0.7388827 | NA | 0.409944 | 30827 |
1 | 801467 | rs61768212 | G | C | 2e-04 | 7e-04 | 0.8360000 | 0.7750970 | NA | 0.193091 | 30014 |
1 | 804759 | rs7526310 | C | T | 1e-04 | 7e-04 | 0.8811000 | 0.8864030 | NA | 0.193890 | 30014 |
1 | 808223 | rs4951933 | G | C | -8e-04 | 6e-04 | 0.1736001 | 0.1824224 | NA | 0.452077 | 26151 |
1 | 808631 | rs11240779 | G | A | -9e-04 | 6e-04 | 0.1308001 | 0.1336144 | NA | 0.453474 | 30560 |
1 | 808928 | rs11240780 | C | T | -8e-04 | 6e-04 | 0.1734998 | 0.1824224 | NA | 0.452276 | 30560 |
1 | 845274 | rs112856858 | G | T | 3e-04 | 6e-04 | 0.6337004 | 0.6170751 | NA | 0.374002 | 26151 |
1 | 845635 | rs117086422 | C | T | 2e-04 | 6e-04 | 0.6944996 | 0.7388827 | NA | 0.158546 | 30560 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51177257 | rs73174437 | C | T | 0.0013 | 0.0014 | 0.3467001 | 0.3531112 | NA | 0.0091853 | 29822 |
22 | 51178607 | rs6010067 | G | C | 0.0004 | 0.0016 | 0.7979001 | 0.8025873 | NA | 0.0814696 | 29822 |
22 | 51180878 | rs6010069 | A | G | -0.0003 | 0.0007 | 0.6435007 | 0.6682351 | NA | 0.1589460 | 26151 |
22 | 51180959 | rs6010070 | A | G | -0.0004 | 0.0007 | 0.5540998 | 0.5677092 | NA | 0.2056710 | 26151 |
22 | 51181685 | rs34756634 | G | A | -0.0001 | 0.0007 | 0.9079999 | 0.8864030 | NA | 0.7118610 | 26151 |
22 | 51181687 | rs9616955 | A | T | 0.0006 | 0.0011 | 0.5655995 | 0.5854409 | NA | 0.0485224 | 26151 |
22 | 51181759 | rs13056621 | A | G | 0.0001 | 0.0007 | 0.9013001 | 0.8864030 | NA | 0.6761180 | 30560 |
22 | 51182090 | rs28516879 | G | A | -0.0003 | 0.0010 | 0.7587994 | 0.7641772 | NA | 0.0467252 | 30111 |
22 | 51185848 | rs3865764 | G | A | -0.0014 | 0.0012 | 0.2454997 | 0.2433450 | NA | 0.9776360 | 29822 |
22 | 51188319 | rs139620215 | T | C | -0.0028 | 0.0022 | 0.2118000 | 0.2031148 | NA | 0.0037939 | 29822 |
1 797440 rs58013264 T C . PASS . ES:SE:LP:SS:ID 0.0001:0.0007:0.0336705:30271:rs58013264
1 798400 rs10900604 A G . PASS . ES:SE:LP:SS:ID 0.0002:0.0006:0.140561:30827:rs10900604
1 798959 rs11240777 G A . PASS . ES:SE:LP:SS:ID 0.0002:0.0006:0.135015:30827:rs11240777
1 801467 rs61768212 G C . PASS . ES:SE:LP:SS:ID 0.0002:0.0007:0.0777937:30014:rs61768212
1 804759 rs7526310 C T . PASS . ES:SE:LP:SS:ID 0.0001:0.0007:0.0549748:30014:rs7526310
1 808223 rs1557576983 G C . PASS . ES:SE:LP:SS:ID -0.0008:0.0006:0.76045:26151:rs1557576983
1 808631 rs11240779 G A . PASS . ES:SE:LP:SS:ID -0.0009:0.0006:0.883392:30560:rs11240779
1 808928 rs1247187939 C T . PASS . ES:SE:LP:SS:ID -0.0008:0.0006:0.760701:30560:rs1247187939
1 845274 rs1324283754 G T . PASS . ES:SE:LP:SS:ID 0.0003:0.0006:0.198116:26151:rs1324283754
1 845635 rs117086422 C T . PASS . ES:SE:LP:SS:ID 0.0002:0.0006:0.158328:30560:rs117086422
1 845938 rs57760052 G A . PASS . ES:SE:LP:SS:ID 0.0002:0.0006:0.116282:30560:rs57760052
1 846078 rs778265812 C T . PASS . ES:SE:LP:SS:ID -0.0003:0.0006:0.210137:30560:rs778265812
1 846398 rs58781670 G A . PASS . ES:SE:LP:SS:ID 0.0001:0.0006:0.0847585:30560:rs58781670
1 846465 rs60454217 C T . PASS . ES:SE:LP:SS:ID 0.0042:0.0019:1.58905:29822:rs60454217
1 846543 rs79396034 G T . PASS . ES:SE:LP:SS:ID 0.0051:0.002:2.00824:26151:rs79396034
1 846808 rs4475691 C T . PASS . ES:SE:LP:SS:ID -0.0003:0.0006:0.180193:30560:rs4475691
1 846864 rs1269142199 G C . PASS . ES:SE:LP:SS:ID -0.0003:0.0006:0.216382:30560:rs1269142199
1 847228 rs3905286 C T . PASS . ES:SE:LP:SS:ID -0.0005:0.0006:0.352031:30560:rs3905286
1 847491 rs1158719307 G A . PASS . ES:SE:LP:SS:ID -0.0004:0.0006:0.281664:30560:rs1158719307
1 848090 rs4246505 G A . PASS . ES:SE:LP:SS:ID -0.0004:0.0006:0.301725:30560:rs4246505
1 848445 rs1156895099 G A . PASS . ES:SE:LP:SS:ID -0.0004:0.0006:0.257746:30560:rs1156895099
1 848456 rs11507767 A G . PASS . ES:SE:LP:SS:ID -0.0004:0.0006:0.264002:30560:rs11507767
1 848738 rs3829741 C T . PASS . ES:SE:LP:SS:ID -0.0004:0.0006:0.312471:30560:rs3829741
1 850062 rs28723578 A T . PASS . ES:SE:LP:SS:ID -0.0004:0.0006:0.272866:30560:rs28723578
1 850123 rs28622257 C T . PASS . ES:SE:LP:SS:ID -0.0004:0.0006:0.30077:30560:rs28622257
1 851190 rs28609852 G A . PASS . ES:SE:LP:SS:ID -0.0004:0.0006:0.267848:30560:rs28609852
1 851204 rs28552953 G C . PASS . ES:SE:LP:SS:ID -0.0003:0.0006:0.208239:30560:rs28552953
1 852664 rs28605311 C T . PASS . ES:SE:LP:SS:ID -0.0006:0.0006:0.450261:30560:rs28605311
1 852758 rs4970462 G C . PASS . ES:SE:LP:SS:ID -0.0006:0.0006:0.440812:30560:rs4970462
1 853239 rs4970380 A G . PASS . ES:SE:LP:SS:ID -0.0005:0.0006:0.417255:30560:rs4970380
1 853805 rs3748591 C T . PASS . ES:SE:LP:SS:ID 0.0046:0.0016:2.36734:29822:rs3748591
1 854250 rs7537756 A G . PASS . ES:SE:LP:SS:ID -0.0006:0.0006:0.442252:30560:rs7537756
1 854429 rs72902552 G A . PASS . ES:SE:LP:SS:ID 0.0046:0.0016:2.35076:29822:rs72902552
1 856436 rs34105146 TG T . PASS . ES:SE:LP:SS:ID -0.0004:0.0007:0.257746:26151:rs34105146
1 856476 rs4040605 A G . PASS . ES:SE:LP:SS:ID -0.0005:0.0005:0.469032:30560:rs4040605
1 857177 rs386627408 T C . PASS . ES:SE:LP:SS:ID 0.0044:0.0016:2.18943:29822:rs386627408
1 858040 rs4970460 C A . PASS . ES:SE:LP:SS:ID -0.0007:0.0006:0.606074:30560:rs4970460
1 858051 rs4970459 C T . PASS . ES:SE:LP:SS:ID -0.0006:0.0006:0.517126:30560:rs4970459
1 858801 rs7418179 A G . PASS . ES:SE:LP:SS:ID 0.0002:0.0006:0.108184:30560:rs7418179
1 859404 rs71509444 C G . PASS . ES:SE:LP:SS:ID -0.0047:0.0017:2.20025:26151:rs71509444
1 859685 rs111572704 G A . PASS . ES:SE:LP:SS:ID -0.0008:0.0006:0.701584:26151:rs111572704
1 859690 rs71509445 C G . PASS . ES:SE:LP:SS:ID -0.0048:0.0018:2.01108:26151:rs71509445
1 859701 rs71509446 C G . PASS . ES:SE:LP:SS:ID -0.0048:0.0018:2.01108:26151:rs71509446
1 859913 rs1187056171 A G . PASS . ES:SE:LP:SS:ID -0.0043:0.0018:1.79751:29822:rs1187056171
1 860416 rs61464428 G A . PASS . ES:SE:LP:SS:ID 0.0002:0.0006:0.144057:30560:rs61464428
1 860461 rs57465118 G A . PASS . ES:SE:LP:SS:ID -0.0045:0.0016:2.35922:29822:rs57465118
1 860521 rs57924093 C A . PASS . ES:SE:LP:SS:ID -0.0045:0.0016:2.35922:29822:rs57924093
1 860688 rs60837925 G A . PASS . ES:SE:LP:SS:ID 0.0002:0.0006:0.148925:30560:rs60837925
1 860854 rs57816555 T C . PASS . ES:SE:LP:SS:ID -0.0053:0.002:2.1528:26151:rs57816555
1 861008 rs28521172 G C . PASS . ES:SE:LP:SS:ID -0.0045:0.0016:2.34921:29822:rs28521172