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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 /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-230/ukb-a-230.vcf.gz \
--ref-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-230/ldsc.txt \
--w-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/
Beginning analysis at Sun Feb 16 01:58:26 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-230/ukb-a-230.vcf.gz ...
Read summary statistics for 10877936 SNPs.
Reading reference panel LD Score from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/[1-22] ...
Read reference panel LD Scores for 1290028 SNPs.
Removing partitioned LD Scores with zero variance.
Reading regression weight LD Score from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/[1-22] ...
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1281483 SNPs remain.
After merging with regression SNP LD, 1281483 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.1145 (0.0055)
Lambda GC: 1.4848
Mean Chi^2: 1.6709
Intercept: 1.0275 (0.0103)
Ratio: 0.041 (0.0154)
Analysis finished at Sun Feb 16 02:00:12 2020
Total time elapsed: 1.0m:45.76s
{
"af_correlation": 0.9533,
"inflation_factor": 1.2953,
"mean_EFFECT": 0.0001,
"n": 274108,
"n_snps": 10877936,
"n_clumped_hits": 68,
"n_p_sig": 8891,
"n_mono": 0,
"n_ns": 0,
"n_mac": 0,
"is_snpid_unique": true,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 0,
"n_miss_AF_reference": 356865,
"n_est": 272973.1834,
"ratio_se_n": 0.9979,
"mean_diff": -0.0001,
"ratio_diff": 112.0286,
"sd_y_est1": 3.2377,
"sd_y_est2": 3.231,
"r2_sum1": 0.1003,
"r2_sum2": 0.0096,
"r2_sum3": 0.0096,
"r2_sum4": 0.0096,
"ldsc_nsnp_merge_refpanel_ld": 1281483,
"ldsc_nsnp_merge_regression_ld": 1281483,
"ldsc_observed_scale_h2_beta": 0.1145,
"ldsc_observed_scale_h2_se": 0.0055,
"ldsc_intercept_beta": 1.0275,
"ldsc_intercept_se": 0.0103,
"ldsc_lambda_gc": 1.4848,
"ldsc_mean_chisq": 1.6709,
"ldsc_ratio": 0.041
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | TRUE |
n | FALSE |
is_snpid_non_unique | FALSE |
mean_EFFECT_nonfinite | FALSE |
mean_EFFECT_05 | FALSE |
mean_EFFECT_01 | FALSE |
mean_chisq | TRUE |
n_p_sig | TRUE |
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 | numeric.mean | numeric.sd | numeric.p0 | numeric.p25 | numeric.p50 | numeric.p75 | numeric.p100 | numeric.hist |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
character | ID | 0 | 1.0000000 | 3 | 58 | 0 | 10877936 | 0 | 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 |
character | ALT | 0 | 1.0000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA |
numeric | CHROM | 0 | 1.0000000 | NA | NA | NA | NA | NA | 8.598638e+00 | 5.745666e+00 | 1.00000e+00 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▃▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.911383e+07 | 5.624931e+07 | 8.28000e+02 | 3.287294e+07 | 6.988889e+07 | 1.148258e+08 | 2.492251e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | 1.391000e-04 | 5.351380e-02 | -6.41356e-01 | -1.636670e-02 | 1.364000e-04 | 1.664900e-02 | 6.307510e-01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 3.766540e-02 | 3.567750e-02 | 8.63600e-03 | 1.067200e-02 | 2.049730e-02 | 5.476360e-02 | 1.952430e-01 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.576510e-01 | 3.003975e-01 | 0.00000e+00 | 1.868620e-01 | 4.427066e-01 | 7.180162e-01 | 1.000000e+00 | ▇▆▆▆▆ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.576504e-01 | 3.003979e-01 | 0.00000e+00 | 1.868608e-01 | 4.427065e-01 | 7.180159e-01 | 9.999999e-01 | ▇▆▆▆▆ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | 1.820865e-01 | 2.503832e-01 | 1.00090e-03 | 6.878700e-03 | 5.191440e-02 | 2.739880e-01 | 9.989990e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 356865 | 0.9671937 | NA | NA | NA | NA | NA | 1.877709e-01 | 2.439191e-01 | 0.00000e+00 | 5.191700e-03 | 7.468050e-02 | 2.873400e-01 | 1.000000e+00 | ▇▂▁▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | 2.741080e+05 | 0.000000e+00 | 2.74108e+05 | 2.741080e+05 | 2.741080e+05 | 2.741080e+05 | 2.741080e+05 | ▁▁▇▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 693731 | rs12238997 | A | G | 0.0022388 | 0.0144276 | 0.8766850 | 0.8766846 | 0.1169260 | 0.1417730 | 274108 |
1 | 717587 | rs144155419 | G | A | 0.0180799 | 0.0385325 | 0.6389193 | 0.6389183 | 0.0143862 | 0.0045926 | 274108 |
1 | 730087 | rs148120343 | T | C | 0.0093797 | 0.0201710 | 0.6419246 | 0.6419231 | 0.0554733 | 0.0127796 | 274108 |
1 | 731718 | rs142557973 | T | C | 0.0019564 | 0.0136909 | 0.8863691 | 0.8863686 | 0.1216580 | 0.1543530 | 274108 |
1 | 734349 | rs141242758 | T | C | 0.0024248 | 0.0136991 | 0.8595050 | 0.8595050 | 0.1215130 | 0.1525560 | 274108 |
1 | 740284 | rs61770167 | C | T | -0.0902314 | 0.0620933 | 0.1461810 | 0.1461798 | 0.0058556 | 0.0023962 | 274108 |
1 | 742813 | rs112573343 | C | T | -0.0532115 | 0.1173840 | 0.6503258 | 0.6503246 | 0.0015525 | 0.1030350 | 274108 |
1 | 753405 | rs3115860 | C | A | -0.0046462 | 0.0130144 | 0.7210876 | 0.7210855 | 0.8706760 | 0.7517970 | 274108 |
1 | 753541 | rs2073813 | G | A | 0.0045688 | 0.0130463 | 0.7261896 | 0.7261889 | 0.1288330 | 0.3019170 | 274108 |
1 | 754182 | rs3131969 | A | G | -0.0041297 | 0.0130002 | 0.7507373 | 0.7507384 | 0.8703180 | 0.6785140 | 274108 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219387 | rs9616832 | T | C | -0.0152597 | 0.0167634 | 0.3626653 | 0.3626650 | 0.0729806 | 0.0654952 | 274108 |
22 | 51219704 | rs147475742 | G | A | 0.0016785 | 0.0224947 | 0.9405191 | 0.9405186 | 0.0418225 | 0.0473243 | 274108 |
22 | 51219766 | rs182321900 | C | T | 0.0285681 | 0.1161650 | 0.8057390 | 0.8057388 | 0.0014546 | NA | 274108 |
22 | 51220088 | rs566371895 | G | A | 0.0143816 | 0.0756266 | 0.8491801 | 0.8491791 | 0.0039843 | 0.0003994 | 274108 |
22 | 51220146 | rs868950473 | C | T | 0.0594496 | 0.1144170 | 0.6033523 | 0.6033514 | 0.0015139 | NA | 274108 |
22 | 51221731 | rs115055839 | T | C | -0.0163622 | 0.0167752 | 0.3293722 | 0.3293716 | 0.0728101 | 0.0625000 | 274108 |
22 | 51223637 | rs375798137 | G | A | 0.0391144 | 0.0197721 | 0.0478994 | 0.0478991 | 0.0540289 | 0.0788738 | 274108 |
22 | 51226692 | rs150189434 | G | A | 0.0507001 | 0.1189370 | 0.6699047 | 0.6699061 | 0.0013983 | 0.0155751 | 274108 |
22 | 51229805 | rs9616985 | T | C | -0.0170554 | 0.0168380 | 0.3111043 | 0.3111025 | 0.0727671 | 0.0730831 | 274108 |
22 | 51237063 | rs3896457 | T | C | -0.0117977 | 0.0102332 | 0.2489580 | 0.2489577 | 0.2968410 | 0.2050720 | 274108 |
1 693731 rs12238997 A G . PASS AF=0.116926 ES:SE:LP:AF:SS:ID 0.00223878:0.0144276:0.0571564:0.116926:274108:rs12238997
1 717587 rs144155419 G A . PASS AF=0.0143862 ES:SE:LP:AF:SS:ID 0.0180799:0.0385325:0.194554:0.0143862:274108:rs144155419
1 730087 rs148120343 T C . PASS AF=0.0554733 ES:SE:LP:AF:SS:ID 0.00937975:0.020171:0.192516:0.0554733:274108:rs148120343
1 731718 rs58276399 T C . PASS AF=0.121658 ES:SE:LP:AF:SS:ID 0.00195644:0.0136909:0.0523854:0.121658:274108:rs58276399
1 734349 rs141242758 T C . PASS AF=0.121513 ES:SE:LP:AF:SS:ID 0.0024248:0.0136991:0.0657516:0.121513:274108:rs141242758
1 740284 rs61770167 C T . PASS AF=0.00585559 ES:SE:LP:AF:SS:ID -0.0902314:0.0620933:0.835109:0.00585559:274108:rs61770167
1 742813 rs112573343 C T . PASS AF=0.0015525 ES:SE:LP:AF:SS:ID -0.0532115:0.117384:0.186869:0.0015525:274108:rs112573343
1 753405 rs3115860 C A . PASS AF=0.870676 ES:SE:LP:AF:SS:ID -0.00464625:0.0130144:0.142012:0.870676:274108:rs3115860
1 753541 rs2073813 G A . PASS AF=0.128833 ES:SE:LP:AF:SS:ID 0.00456881:0.0130463:0.13895:0.128833:274108:rs2073813
1 754182 rs3131969 A G . PASS AF=0.870318 ES:SE:LP:AF:SS:ID -0.00412972:0.0130002:0.124512:0.870318:274108:rs3131969
1 754192 rs3131968 A G . PASS AF=0.870409 ES:SE:LP:AF:SS:ID -0.00385926:0.0130065:0.115384:0.870409:274108:rs3131968
1 754334 rs3131967 T C . PASS AF=0.870037 ES:SE:LP:AF:SS:ID -0.00426992:0.0129997:0.129267:0.870037:274108:rs3131967
1 754433 rs150578204 G A . PASS AF=0.00465304 ES:SE:LP:AF:SS:ID 0.0443973:0.0663436:0.298114:0.00465304:274108:rs150578204
1 754458 rs142682604 G T . PASS AF=0.00464711 ES:SE:LP:AF:SS:ID 0.0459403:0.0665293:0.309925:0.00464711:274108:rs142682604
1 755435 rs184270342 T G . PASS AF=0.00590897 ES:SE:LP:AF:SS:ID -0.0160379:0.0644979:0.094946:0.00590897:274108:rs184270342
1 755890 rs3115858 A T . PASS AF=0.870329 ES:SE:LP:AF:SS:ID -0.00484571:0.0129785:0.149429:0.870329:274108:rs3115858
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1 757734 rs4951929 C T . PASS AF=0.870219 ES:SE:LP:AF:SS:ID -0.00580915:0.0129579:0.184469:0.870219:274108:rs4951929
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1 758626 rs3131954 C T . PASS AF=0.870396 ES:SE:LP:AF:SS:ID -0.00490659:0.0129922:0.151388:0.870396:274108:rs3131954
1 761732 rs2286139 C T . PASS AF=0.867743 ES:SE:LP:AF:SS:ID -0.00670453:0.0129297:0.218903:0.867743:274108:rs2286139
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1 769223 rs60320384 C G . PASS AF=0.128651 ES:SE:LP:AF:SS:ID 0.00553907:0.0130281:0.173461:0.128651:274108:rs60320384
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1 770377 rs112563271 A T . PASS AF=0.00692321 ES:SE:LP:AF:SS:ID 0.0395361:0.0529065:0.34209:0.00692321:274108:rs112563271
1 771823 rs2977605 T C . PASS AF=0.869934 ES:SE:LP:AF:SS:ID -0.00630339:0.0129697:0.202759:0.869934:274108:rs2977605
1 771967 rs59066358 G A . PASS AF=0.128709 ES:SE:LP:AF:SS:ID 0.00552759:0.0130223:0.173134:0.128709:274108:rs59066358
1 772755 rs2905039 A C . PASS AF=0.870112 ES:SE:LP:AF:SS:ID -0.00638111:0.0129703:0.205697:0.870112:274108:rs2905039
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1 777122 rs2980319 A T . PASS AF=0.871122 ES:SE:LP:AF:SS:ID -0.00304684:0.0129932:0.0890556:0.871122:274108:rs2980319
1 777232 rs112618790 C T . PASS AF=0.0961319 ES:SE:LP:AF:SS:ID 0.00208252:0.0150081:0.0507857:0.0961319:274108:rs112618790
1 778745 rs1055606 A G . PASS AF=0.127871 ES:SE:LP:AF:SS:ID 0.00265398:0.0130359:0.0764068:0.127871:274108:rs1055606
1 779322 rs4040617 A G . PASS AF=0.127984 ES:SE:LP:AF:SS:ID 0.00302676:0.0130181:0.0882321:0.127984:274108:rs4040617
1 780785 rs2977612 T A . PASS AF=0.870455 ES:SE:LP:AF:SS:ID -0.00297064:0.0129709:0.0867951:0.870455:274108:rs2977612
1 781367 rs149821290 A C . PASS AF=0.00989772 ES:SE:LP:AF:SS:ID -0.0791437:0.0461959:1.06211:0.00989772:274108:rs149821290
1 781845 rs61768199 A G . PASS AF=0.1044 ES:SE:LP:AF:SS:ID -0.00192647:0.0145945:0.0481842:0.1044:274108:rs61768199
1 782721 rs185280546 G A . PASS AF=0.0143713 ES:SE:LP:AF:SS:ID -0.00246452:0.0395053:0.0221589:0.0143713:274108:rs185280546
1 782981 rs6594026 C T . PASS AF=0.128338 ES:SE:LP:AF:SS:ID 0.000785019:0.0130252:0.02139:0.128338:274108:rs6594026
1 783193 rs145767270 G C . PASS AF=0.0143639 ES:SE:LP:AF:SS:ID 0.00298526:0.0396571:0.0268745:0.0143639:274108:rs145767270
1 783194 rs138555831 G T . PASS AF=0.0143713 ES:SE:LP:AF:SS:ID 0.00305438:0.0396522:0.0275194:0.0143713:274108:rs138555831
1 783711 rs184266993 G A . PASS AF=0.00541372 ES:SE:LP:AF:SS:ID -0.0647919:0.063053:0.516914:0.00541372:274108:rs184266993
1 785050 rs2905062 G A . PASS AF=0.87014 ES:SE:LP:AF:SS:ID -0.00333234:0.0129735:0.0983837:0.87014:274108:rs2905062
1 785989 rs2980300 T C . PASS AF=0.87009 ES:SE:LP:AF:SS:ID -0.00309188:0.0129817:0.0905793:0.87009:274108:rs2980300