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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/ieu-a-import/processed/ieu-a-982/ieu-a-982.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/ieu-a-import/processed/ieu-a-982/ldsc.txt \
--w-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/
Beginning analysis at Tue Feb 4 16:22:05 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ieu-a-import/processed/ieu-a-982/ieu-a-982.vcf.gz ...
Read summary statistics for 9282363 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, 1170690 SNPs remain.
After merging with regression SNP LD, 1170690 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.1345 (0.0148)
Lambda GC: 1.1144
Mean Chi^2: 1.1421
Intercept: 1.0267 (0.0079)
Ratio: 0.1879 (0.0556)
Analysis finished at Tue Feb 4 16:23:38 2020
Total time elapsed: 1.0m:32.59s
{
"af_correlation": 0.9825,
"inflation_factor": 1.0276,
"mean_EFFECT": -0.0001,
"n": 44731,
"n_snps": 9282363,
"n_clumped_hits": 24,
"n_p_sig": 1080,
"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": 253400,
"n_miss_AF_reference": 309158,
"n_est": 38597.9902,
"ratio_se_n": 0.9289,
"mean_diff": 1.0939e-06,
"ratio_diff": 0.0382,
"sd_y_est1": 1.417,
"sd_y_est2": 1.3163,
"r2_sum1": 0.0446,
"r2_sum2": 0.0222,
"r2_sum3": 0.0257,
"r2_sum4": 0.0257,
"ldsc_nsnp_merge_refpanel_ld": 1170690,
"ldsc_nsnp_merge_regression_ld": 1170690,
"ldsc_observed_scale_h2_beta": 0.1345,
"ldsc_observed_scale_h2_se": 0.0148,
"ldsc_intercept_beta": 1.0267,
"ldsc_intercept_se": 0.0079,
"ldsc_lambda_gc": 1.1144,
"ldsc_mean_chisq": 1.1421,
"ldsc_ratio": 0.1879
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | FALSE |
n | FALSE |
is_snpid_non_unique | FALSE |
mean_EFFECT_nonfinite | FALSE |
mean_EFFECT_05 | FALSE |
mean_EFFECT_01 | FALSE |
mean_chisq | FALSE |
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 | 57 | 0 | 9282361 | 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 | 8.741171e+00 | 5.840027e+00 | 1.0000e+00 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.300000e+01 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.827971e+07 | 5.631421e+07 | 8.2800e+02 | 3.208554e+07 | 6.846187e+07 | 1.139365e+08 | 2.492391e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | -1.273000e-04 | 3.214310e-02 | -1.2700e+00 | -1.211100e-02 | -1.790000e-04 | 1.173400e-02 | 1.342360e+00 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 2.454840e-02 | 1.993180e-02 | 1.9500e-04 | 1.028800e-02 | 1.610900e-02 | 3.250100e-02 | 5.770230e-01 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.956376e-01 | 2.902627e-01 | 0.0000e+00 | 2.435337e-01 | 4.941366e-01 | 7.471779e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.881383e-01 | 2.921555e-01 | 0.0000e+00 | 2.324671e-01 | 4.838549e-01 | 7.413405e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF | 253400 | 0.9727009 | NA | NA | NA | NA | NA | 2.337870e-01 | 2.660649e-01 | 7.9600e-05 | 2.458230e-02 | 1.184570e-01 | 3.680990e-01 | 9.999200e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 309158 | 0.9666940 | NA | NA | NA | NA | NA | 2.344785e-01 | 2.643032e-01 | 0.0000e+00 | 1.936900e-02 | 1.279950e-01 | 3.694090e-01 | 1.000000e+00 | ▇▂▂▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.473100e+04 | 0.000000e+00 | 4.4731e+04 | 4.473100e+04 | 4.473100e+04 | 4.473100e+04 | 4.473100e+04 | ▁▁▇▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 51479 | rs116400033 | T | A | 0.004911 | 0.019236 | 0.8030900 | 0.7984894 | 0.175736 | 0.1281950 | 44731 |
1 | 52058 | rs62637813 | G | C | 0.020419 | 0.057827 | 0.7302137 | 0.7240098 | NA | NA | 44731 |
1 | 54421 | rs146477069 | A | G | 0.031451 | 0.051528 | 0.5511172 | 0.5416186 | NA | NA | 44731 |
1 | 54490 | rs141149254 | G | A | -0.004011 | 0.020008 | 0.8447751 | 0.8411132 | 0.125457 | 0.0960463 | 44731 |
1 | 54676 | rs2462492 | C | T | 0.047952 | 0.042411 | 0.2694728 | 0.2582024 | NA | NA | 44731 |
1 | 54753 | rs143174675 | T | G | -0.057749 | 0.048486 | 0.2447113 | 0.2336360 | NA | NA | 44731 |
1 | 55164 | rs3091274 | C | A | 0.001285 | 0.018672 | 0.9463910 | 0.9451332 | 0.960700 | 0.9233230 | 44731 |
1 | 55299 | rs10399749 | C | T | 0.016499 | 0.017334 | 0.3525462 | 0.3411838 | NA | NA | 44731 |
1 | 55326 | rs3107975 | T | C | -0.035331 | 0.068901 | 0.6165254 | 0.6081058 | 0.028401 | 0.0459265 | 44731 |
1 | 58814 | rs114420996 | G | A | -0.060436 | 0.034647 | 0.0884525 | 0.0811006 | 0.101034 | 0.1090260 | 44731 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51227891 | rs6010091 | G | A | 0.006149 | 0.018749 | 0.7487365 | 0.7429388 | 0.4236280 | 0.4039540 | 44731 |
22 | 51229805 | rs9616985 | T | C | 0.012784 | 0.024161 | 0.6053367 | 0.5967242 | 0.0715195 | 0.0730831 | 44731 |
22 | 51229813 | rs191731586 | T | C | 0.001512 | 0.025681 | 0.9541349 | 0.9530507 | 0.0052506 | 0.0057907 | 44731 |
22 | 51229855 | rs144549712 | G | A | 0.025790 | 0.057232 | 0.6598831 | 0.6522620 | 0.1306280 | 0.1160140 | 44731 |
22 | 51234677 | rs189571549 | A | C | -0.011509 | 0.034063 | 0.7414195 | 0.7354582 | 0.0098648 | 0.0227636 | 44731 |
23 | 35747397 | rs74987454 | T | C | 0.142038 | 0.078800 | 0.0783394 | 0.0714648 | NA | NA | 44731 |
23 | 50040891 | rs192267219 | C | T | -0.018269 | 0.088388 | 0.8400130 | 0.8362512 | NA | 0.0222517 | 44731 |
23 | 75822996 | rs147134110 | C | T | -0.016507 | 0.031351 | 0.6071192 | 0.5985254 | 0.0243437 | 0.0773510 | 44731 |
23 | 100784211 | rs188350543 | C | A | -0.015681 | 0.011143 | 0.1692949 | 0.1593529 | 0.7770880 | 0.6498010 | 44731 |
23 | 133445361 | rs112934402 | T | C | -0.115833 | 0.100743 | 0.2614442 | 0.2502316 | 0.0037391 | NA | 44731 |
1 51479 rs116400033 T A . PASS AF=0.175736 ES:SE:LP:AF:SS:ID 0.004911:0.019236:0.0952358:0.175736:44731:rs116400033
1 52058 rs62637813 G C . PASS . ES:SE:LP:SS:ID 0.020419:0.057827:0.13655:44731:rs62637813
1 54421 rs146477069 A G . PASS . ES:SE:LP:SS:ID 0.031451:0.051528:0.258756:44731:rs146477069
1 54490 rs141149254 G A . PASS AF=0.125457 ES:SE:LP:AF:SS:ID -0.004011:0.020008:0.0732589:0.125457:44731:rs141149254
1 54676 rs2462492 C T . PASS . ES:SE:LP:SS:ID 0.047952:0.042411:0.569485:44731:rs2462492
1 54753 rs143174675 T G . PASS . ES:SE:LP:SS:ID -0.057749:0.048486:0.611346:44731:rs143174675
1 55164 rs3091274 C A . PASS AF=0.9607 ES:SE:LP:AF:SS:ID 0.001285:0.018672:0.0239294:0.9607:44731:rs3091274
1 55299 rs10399749 C T . PASS . ES:SE:LP:SS:ID 0.016499:0.017334:0.452784:44731:rs10399749
1 55326 rs3107975 T C . PASS AF=0.028401 ES:SE:LP:AF:SS:ID -0.035331:0.068901:0.210049:0.028401:44731:rs3107975
1 58814 rs114420996 G A . PASS AF=0.101034 ES:SE:LP:AF:SS:ID -0.060436:0.034647:1.05329:0.101034:44731:rs114420996
1 61987 rs76735897 A G . PASS . ES:SE:LP:SS:ID 0.013263:0.016791:0.356095:44731:rs76735897
1 61989 rs77573425 G C . PASS . ES:SE:LP:SS:ID 0.012347:0.016792:0.325403:44731:rs77573425
1 66162 rs62639105 A T . PASS . ES:SE:LP:SS:ID 0.020242:0.017057:0.608289:44731:rs62639105
1 66507 rs12401368 T A . PASS . ES:SE:LP:SS:ID -0.017531:0.024781:0.31013:44731:rs12401368
1 73841 rs143773730 C T . PASS . ES:SE:LP:SS:ID 0.044073:0.039691:0.555735:44731:rs143773730
1 77961 rs78385339 G A . PASS . ES:SE:LP:SS:ID 0.065072:0.073157:0.414537:44731:rs78385339
1 79772 rs147215883 C G . PASS . ES:SE:LP:SS:ID -0.035839:0.033016:0.539007:44731:rs147215883
1 82163 rs139113303 G A . PASS AF=0.0603819 ES:SE:LP:AF:SS:ID -0.091367:0.095912:0.453246:0.0603819:44731:rs139113303
1 82249 rs1851945 A G . PASS . ES:SE:LP:SS:ID -0.0194:0.026861:0.318216:44731:rs1851945
1 82303 rs3871776 T C . PASS . ES:SE:LP:SS:ID 0.011094:0.032515:0.131378:44731:rs3871776
1 82316 rs4030305 A C . PASS . ES:SE:LP:SS:ID 0.061821:0.054722:0.568881:44731:rs4030305
1 82609 rs149189449 C G . PASS AF=0.0604614 ES:SE:LP:AF:SS:ID 0.010659:0.035008:0.115665:0.0604614:44731:rs149189449
1 82676 rs185237834 T G . PASS . ES:SE:LP:SS:ID -0.019841:0.034215:0.243237:44731:rs185237834
1 82734 rs4030331 T C . PASS . ES:SE:LP:SS:ID -0.032103:0.022044:0.809921:44731:rs4030331
1 84002 rs28850140 G A . PASS . ES:SE:LP:SS:ID 0.111616:0.040308:2.1638:44731:rs28850140
1 84010 rs186443818 G A . PASS . ES:SE:LP:SS:ID -0.092391:0.095565:0.462118:44731:rs186443818
1 84244 rs191297051 A C . PASS . ES:SE:LP:SS:ID -0.017443:0.034171:0.208929:44731:rs191297051
1 85597 rs192472955 A C . PASS . ES:SE:LP:SS:ID 0.012686:0.017349:0.323173:44731:rs192472955
1 86018 rs142878000 C G . PASS . ES:SE:LP:SS:ID -0.023955:0.032716:0.323712:44731:rs142878000
1 86028 rs114608975 T C . PASS AF=0.0540971 ES:SE:LP:AF:SS:ID 0.003034:0.02725:0.0393476:0.0540971:44731:rs114608975
1 86065 rs116504101 G C . PASS AF=0.0630072 ES:SE:LP:AF:SS:ID 0.005445:0.027206:0.0731325:0.0630072:44731:rs116504101
1 86303 rs2949417 G T . PASS . ES:SE:LP:SS:ID -0.022184:0.032828:0.293051:44731:rs2949417
1 86331 rs115209712 A G . PASS AF=0.110183 ES:SE:LP:AF:SS:ID -0.019003:0.032836:0.242634:0.110183:44731:rs115209712
1 87021 rs188486692 T C . PASS AF=0.00906921 ES:SE:LP:AF:SS:ID 0.044805:0.090942:0.200374:0.00906921:44731:rs188486692
1 87190 rs1524602 G A . PASS . ES:SE:LP:SS:ID -0.043418:0.029811:0.809996:44731:rs1524602
1 87409 rs139490478 C T . PASS AF=0.0637232 ES:SE:LP:AF:SS:ID -0.091827:0.099278:0.436124:0.0637232:44731:rs139490478
1 88169 rs940550 C T . PASS AF=0.24463 ES:SE:LP:AF:SS:ID -0.033078:0.030123:0.547444:0.24463:44731:rs940550
1 88172 rs940551 G A . PASS AF=0.0574383 ES:SE:LP:AF:SS:ID 0.010598:0.032771:0.123711:0.0574383:44731:rs940551
1 88177 rs143215837 G C . PASS AF=0.0560064 ES:SE:LP:AF:SS:ID 0.044709:0.040623:0.549123:0.0560064:44731:rs143215837
1 88188 rs148331237 C A . PASS AF=0.00445505 ES:SE:LP:AF:SS:ID -0.005295:0.087968:0.0208597:0.00445505:44731:rs148331237
1 88236 rs186918018 C T . PASS AF=0.00731901 ES:SE:LP:AF:SS:ID -0.055716:0.093503:0.251335:0.00731901:44731:rs186918018
1 88316 rs113759966 G A . PASS AF=0.0566428 ES:SE:LP:AF:SS:ID 0.01737:0.032384:0.221564:0.0566428:44731:rs113759966
1 88338 rs55700207 G A . PASS AF=0.0881464 ES:SE:LP:AF:SS:ID -0.048467:0.038402:0.662144:0.0881464:44731:rs55700207
1 88370 rs185487977 G A . PASS AF=0.00238663 ES:SE:LP:AF:SS:ID -0.14133:0.137079:0.503135:0.00238663:44731:rs185487977
1 88710 rs186575039 C G . PASS AF=0.0631663 ES:SE:LP:AF:SS:ID -0.078864:0.099099:0.359488:0.0631663:44731:rs186575039
1 89946 rs138808727 A T . PASS AF=0.170485 ES:SE:LP:AF:SS:ID 0.006396:0.019205:0.127845:0.170485:44731:rs138808727
1 91190 rs143856811 G A . PASS AF=0.0647574 ES:SE:LP:AF:SS:ID -0.091054:0.091034:0.483305:0.0647574:44731:rs143856811
1 92633 rs149776517 C T . PASS AF=0.0186953 ES:SE:LP:AF:SS:ID 0.038471:0.132255:0.109947:0.0186953:44731:rs149776517
1 92858 rs147061536 G T . PASS AF=0.183055 ES:SE:LP:AF:SS:ID 0.009949:0.019255:0.211939:0.183055:44731:rs147061536
1 98929 rs12184306 A G . PASS . ES:SE:LP:SS:ID 0.015877:0.017606:0.421981:44731:rs12184306