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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-980/ieu-a-980.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-980/ldsc.txt \
--w-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/
Beginning analysis at Wed Feb 5 09:13:42 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ieu-a-import/processed/ieu-a-980/ieu-a-980.vcf.gz ...
Read summary statistics for 9280966 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, 1170827 SNPs remain.
After merging with regression SNP LD, 1170827 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.1269 (0.0145)
Lambda GC: 1.1069
Mean Chi^2: 1.1463
Intercept: 1.0228 (0.0079)
Ratio: 0.1555 (0.0537)
Analysis finished at Wed Feb 5 09:15:12 2020
Total time elapsed: 1.0m:30.15s
{
"af_correlation": 0.9825,
"inflation_factor": 1.029,
"mean_EFFECT": -0.0001,
"n": 49988,
"n_snps": 9280966,
"n_clumped_hits": 21,
"n_p_sig": 869,
"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": 253347,
"n_miss_AF_reference": 309164,
"n_est": 42800.9641,
"ratio_se_n": 0.9253,
"mean_diff": -0,
"ratio_diff": 0.8153,
"sd_y_est1": 1.2928,
"sd_y_est2": 1.1963,
"r2_sum1": 0.0308,
"r2_sum2": 0.0184,
"r2_sum3": 0.0215,
"r2_sum4": 0.0217,
"ldsc_nsnp_merge_refpanel_ld": 1170827,
"ldsc_nsnp_merge_regression_ld": 1170827,
"ldsc_observed_scale_h2_beta": 0.1269,
"ldsc_observed_scale_h2_se": 0.0145,
"ldsc_intercept_beta": 1.0228,
"ldsc_intercept_se": 0.0079,
"ldsc_lambda_gc": 1.1069,
"ldsc_mean_chisq": 1.1463,
"ldsc_ratio": 0.1558
}
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 | 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 | numeric.mean | numeric.sd | numeric.p0 | numeric.p25 | numeric.p50 | numeric.p75 | numeric.p100 | numeric.hist |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
character | ID | 0 | 1.0000000 | 3 | 57 | 0 | 9280964 | 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 | 8.739298e+00 | 5.837432e+00 | 1.00000e+00 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.300000e+01 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.828070e+07 | 5.631068e+07 | 8.28000e+02 | 3.209398e+07 | 6.846330e+07 | 1.139317e+08 | 2.492391e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | -6.680000e-05 | 2.784440e-02 | -1.12184e+00 | -1.038700e-02 | -7.600000e-05 | 1.023300e-02 | 1.044640e+00 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 2.123530e-02 | 1.742150e-02 | 3.95000e-04 | 8.873000e-03 | 1.390800e-02 | 2.808600e-02 | 4.253630e-01 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.949877e-01 | 2.905118e-01 | 0.00000e+00 | 2.416490e-01 | 4.938545e-01 | 7.469216e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.880778e-01 | 2.922561e-01 | 0.00000e+00 | 2.314686e-01 | 4.843782e-01 | 7.415427e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF | 253347 | 0.9727025 | NA | NA | NA | NA | NA | 2.338344e-01 | 2.660501e-01 | 7.96000e-05 | 2.458230e-02 | 1.185360e-01 | 3.681780e-01 | 9.999200e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 309164 | 0.9666884 | NA | NA | NA | NA | NA | 2.345222e-01 | 2.642879e-01 | 0.00000e+00 | 1.936900e-02 | 1.279950e-01 | 3.694090e-01 | 1.000000e+00 | ▇▂▂▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.998800e+04 | 0.000000e+00 | 4.99880e+04 | 4.998800e+04 | 4.998800e+04 | 4.998800e+04 | 4.998800e+04 | ▁▁▇▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 51479 | rs116400033 | T | A | 0.010024 | 0.018989 | 0.6055054 | 0.5975795 | 0.175736 | 0.1281950 | 49988 |
1 | 52058 | rs62637813 | G | C | 0.105988 | 0.065444 | 0.1130420 | 0.1053350 | NA | NA | 49988 |
1 | 54421 | rs146477069 | A | G | 0.106444 | 0.047875 | 0.0296149 | 0.0261906 | NA | NA | 49988 |
1 | 54490 | rs141149254 | G | A | 0.001673 | 0.019823 | 0.9341500 | 0.9327409 | 0.125457 | 0.0960463 | 49988 |
1 | 54676 | rs2462492 | C | T | 0.033397 | 0.039605 | 0.4093172 | 0.3990875 | NA | NA | 49988 |
1 | 54753 | rs143174675 | T | G | 0.032019 | 0.046679 | 0.5021321 | 0.4927509 | NA | NA | 49988 |
1 | 55164 | rs3091274 | C | A | -0.010351 | 0.016214 | 0.5322063 | 0.5232140 | 0.960700 | 0.9233230 | 49988 |
1 | 55299 | rs10399749 | C | T | -0.023400 | 0.017149 | 0.1818210 | 0.1724068 | NA | NA | 49988 |
1 | 55326 | rs3107975 | T | C | 0.082553 | 0.066434 | 0.2240139 | 0.2140036 | 0.028401 | 0.0459265 | 49988 |
1 | 58814 | rs114420996 | G | A | -0.015995 | 0.032037 | 0.6252044 | 0.6175917 | 0.101034 | 0.1090260 | 49988 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51227891 | rs6010091 | G | A | 0.019188 | 0.018546 | 0.3113738 | 0.3008480 | 0.4236280 | 0.4039540 | 49988 |
22 | 51229805 | rs9616985 | T | C | 0.038994 | 0.023551 | 0.1052059 | 0.0977773 | 0.0715195 | 0.0730831 | 49988 |
22 | 51229813 | rs191731586 | T | C | 0.014295 | 0.021245 | 0.5103064 | 0.5010337 | 0.0052506 | 0.0057907 | 49988 |
22 | 51229855 | rs144549712 | G | A | 0.008556 | 0.052992 | 0.8744470 | 0.8717324 | 0.1306280 | 0.1160140 | 49988 |
22 | 51234677 | rs189571549 | A | C | 0.018367 | 0.028846 | 0.5332919 | 0.5243033 | 0.0098648 | 0.0227636 | 49988 |
23 | 35747397 | rs74987454 | T | C | 0.038693 | 0.078348 | 0.6289556 | 0.6214045 | NA | NA | 49988 |
23 | 50040891 | rs192267219 | C | T | 0.050430 | 0.080282 | 0.5388154 | 0.5298987 | NA | 0.0222517 | 49988 |
23 | 75822996 | rs147134110 | C | T | 0.021534 | 0.030359 | 0.4876655 | 0.4781309 | 0.0243437 | 0.0773510 | 49988 |
23 | 100784211 | rs188350543 | C | A | -0.001614 | 0.010167 | 0.8765639 | 0.8738667 | 0.7770880 | 0.6498010 | 49988 |
23 | 133445361 | rs112934402 | T | C | -0.206403 | 0.099276 | 0.0419382 | 0.0376098 | 0.0037391 | NA | 49988 |
1 51479 rs116400033 T A . PASS AF=0.175736 ES:SE:LP:AF:SS:ID 0.010024:0.018989:0.217882:0.175736:49988:rs116400033
1 52058 rs62637813 G C . PASS . ES:SE:LP:SS:ID 0.105988:0.065444:0.94676:49988:rs62637813
1 54421 rs146477069 A G . PASS . ES:SE:LP:SS:ID 0.106444:0.047875:1.52849:49988:rs146477069
1 54490 rs141149254 G A . PASS AF=0.125457 ES:SE:LP:AF:SS:ID 0.001673:0.019823:0.0295834:0.125457:49988:rs141149254
1 54676 rs2462492 C T . PASS . ES:SE:LP:SS:ID 0.033397:0.039605:0.38794:49988:rs2462492
1 54753 rs143174675 T G . PASS . ES:SE:LP:SS:ID 0.032019:0.046679:0.299182:49988:rs143174675
1 55164 rs3091274 C A . PASS AF=0.9607 ES:SE:LP:AF:SS:ID -0.010351:0.016214:0.27392:0.9607:49988:rs3091274
1 55299 rs10399749 C T . PASS . ES:SE:LP:SS:ID -0.0234:0.017149:0.740356:49988:rs10399749
1 55326 rs3107975 T C . PASS AF=0.028401 ES:SE:LP:AF:SS:ID 0.082553:0.066434:0.649725:0.028401:49988:rs3107975
1 58814 rs114420996 G A . PASS AF=0.101034 ES:SE:LP:AF:SS:ID -0.015995:0.032037:0.203978:0.101034:49988:rs114420996
1 61987 rs76735897 A G . PASS . ES:SE:LP:SS:ID -0.018727:0.01641:0.578163:49988:rs76735897
1 61989 rs77573425 G C . PASS . ES:SE:LP:SS:ID -0.020934:0.016416:0.673459:49988:rs77573425
1 66162 rs62639105 A T . PASS . ES:SE:LP:SS:ID -0.017768:0.01671:0.525602:49988:rs62639105
1 66507 rs12401368 T A . PASS . ES:SE:LP:SS:ID 0.029618:0.024993:0.608671:49988:rs12401368
1 73841 rs143773730 C T . PASS . ES:SE:LP:SS:ID 0.022118:0.037043:0.252517:49988:rs143773730
1 77961 rs78385339 G A . PASS . ES:SE:LP:SS:ID 0.111577:0.0777:0.795926:49988:rs78385339
1 79772 rs147215883 C G . PASS . ES:SE:LP:SS:ID -0.006603:0.029662:0.0821963:49988:rs147215883
1 82163 rs139113303 G A . PASS AF=0.0603819 ES:SE:LP:AF:SS:ID -0.143593:0.08818:0.954364:0.0603819:49988:rs139113303
1 82249 rs1851945 A G . PASS . ES:SE:LP:SS:ID 0.012287:0.026436:0.187565:49988:rs1851945
1 82303 rs3871776 T C . PASS . ES:SE:LP:SS:ID 0.029117:0.032463:0.42005:49988:rs3871776
1 82316 rs4030305 A C . PASS . ES:SE:LP:SS:ID 0.058093:0.053918:0.534968:49988:rs4030305
1 82609 rs149189449 C G . PASS AF=0.0604614 ES:SE:LP:AF:SS:ID -0.002156:0.034558:0.0216784:0.0604614:49988:rs149189449
1 82676 rs185237834 T G . PASS . ES:SE:LP:SS:ID -0.016548:0.034247:0.196275:49988:rs185237834
1 82734 rs4030331 T C . PASS . ES:SE:LP:SS:ID 0.004701:0.021638:0.0800714:49988:rs4030331
1 84002 rs28850140 G A . PASS . ES:SE:LP:SS:ID 0.06668:0.036419:1.13537:49988:rs28850140
1 84010 rs186443818 G A . PASS . ES:SE:LP:SS:ID 0.050587:0.085981:0.248068:49988:rs186443818
1 84244 rs191297051 A C . PASS . ES:SE:LP:SS:ID -0.030961:0.034169:0.425636:49988:rs191297051
1 85597 rs192472955 A C . PASS . ES:SE:LP:SS:ID -0.033066:0.017107:1.23209:49988:rs192472955
1 86018 rs142878000 C G . PASS . ES:SE:LP:SS:ID 0.003581:0.032745:0.0386924:49988:rs142878000
1 86028 rs114608975 T C . PASS AF=0.0540971 ES:SE:LP:AF:SS:ID 0.013489:0.025429:0.219145:0.0540971:49988:rs114608975
1 86065 rs116504101 G C . PASS AF=0.0630072 ES:SE:LP:AF:SS:ID 0.01292:0.02536:0.208898:0.0630072:49988:rs116504101
1 86303 rs2949417 G T . PASS . ES:SE:LP:SS:ID -0.007598:0.032841:0.0857039:49988:rs2949417
1 86331 rs115209712 A G . PASS AF=0.110183 ES:SE:LP:AF:SS:ID -0.006308:0.032861:0.0700725:0.110183:49988:rs115209712
1 87021 rs188486692 T C . PASS AF=0.00906921 ES:SE:LP:AF:SS:ID 0.092191:0.084298:0.545817:0.00906921:49988:rs188486692
1 87190 rs1524602 G A . PASS . ES:SE:LP:SS:ID 0.01431:0.040933:0.135308:49988:rs1524602
1 87409 rs139490478 C T . PASS AF=0.0637232 ES:SE:LP:AF:SS:ID -0.112726:0.088673:0.670555:0.0637232:49988:rs139490478
1 88169 rs940550 C T . PASS AF=0.24463 ES:SE:LP:AF:SS:ID 0.010901:0.041232:0.0991557:0.24463:49988:rs940550
1 88172 rs940551 G A . PASS AF=0.0574383 ES:SE:LP:AF:SS:ID 0.002437:0.030661:0.0278041:0.0574383:49988:rs940551
1 88177 rs143215837 G C . PASS AF=0.0560064 ES:SE:LP:AF:SS:ID -0.007118:0.039711:0.0651144:0.0560064:49988:rs143215837
1 88188 rs148331237 C A . PASS AF=0.00445505 ES:SE:LP:AF:SS:ID 0.083469:0.078137:0.528855:0.00445505:49988:rs148331237
1 88236 rs186918018 C T . PASS AF=0.00731901 ES:SE:LP:AF:SS:ID -0.081816:0.080001:0.498978:0.00731901:49988:rs186918018
1 88316 rs113759966 G A . PASS AF=0.0566428 ES:SE:LP:AF:SS:ID 0.00986:0.030391:0.124416:0.0566428:49988:rs113759966
1 88338 rs55700207 G A . PASS AF=0.0881464 ES:SE:LP:AF:SS:ID -0.007863:0.035621:0.0814518:0.0881464:49988:rs55700207
1 88370 rs185487977 G A . PASS AF=0.00238663 ES:SE:LP:AF:SS:ID 0.038143:0.135988:0.105829:0.00238663:49988:rs185487977
1 88710 rs186575039 C G . PASS AF=0.0631663 ES:SE:LP:AF:SS:ID -0.106486:0.08935:0.613424:0.0631663:49988:rs186575039
1 89946 rs138808727 A T . PASS AF=0.170485 ES:SE:LP:AF:SS:ID 0.004587:0.018915:0.0902189:0.170485:49988:rs138808727
1 91190 rs143856811 G A . PASS AF=0.0647574 ES:SE:LP:AF:SS:ID -0.125627:0.083004:0.858184:0.0647574:49988:rs143856811
1 92633 rs149776517 C T . PASS AF=0.0186953 ES:SE:LP:AF:SS:ID -0.109606:0.116984:0.444587:0.0186953:49988:rs149776517
1 92858 rs147061536 G T . PASS AF=0.183055 ES:SE:LP:AF:SS:ID 0.004052:0.018975:0.0785919:0.183055:49988:rs147061536
1 98929 rs12184306 A G . PASS . ES:SE:LP:SS:ID -0.028247:0.017297:0.958347:49988:rs12184306