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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/sun/processed/PROT-a-2636/PROT-a-2636.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/sun/processed/PROT-a-2636/ldsc.txt \
--w-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/
Beginning analysis at Mon Oct 28 20:46:13 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/sun/processed/PROT-a-2636/PROT-a-2636.vcf.gz ...
Read summary statistics for 10265284 SNPs.
Dropped 20 SNPs with duplicated rs numbers.
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, 1280408 SNPs remain.
After merging with regression SNP LD, 1280408 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.145 (0.1358)
Lambda GC: 1.0188
Mean Chi^2: 1.0113
Intercept: 1.0017 (0.0069)
Ratio: 0.1549 (0.6109)
Analysis finished at Mon Oct 28 20:47:41 2019
Total time elapsed: 1.0m:28.35s
{
"af_correlation": 0.9467,
"inflation_factor": 0.9945,
"mean_EFFECT": -0,
"n": "-Inf",
"n_snps": 10265284,
"n_clumped_hits": 0,
"n_p_sig": 0,
"n_mono": 0,
"n_ns": 884453,
"n_mac": 0,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 277,
"n_miss_AF_reference": 477442,
"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": 1280408,
"ldsc_nsnp_merge_regression_ld": 1280408,
"ldsc_observed_scale_h2_beta": 0.145,
"ldsc_observed_scale_h2_se": 0.1358,
"ldsc_intercept_beta": 1.0017,
"ldsc_intercept_se": 0.0069,
"ldsc_lambda_gc": 1.0188,
"ldsc_mean_chisq": 1.0113,
"ldsc_ratio": 0.1504
}
name | value |
---|---|
name | value |
af_correlation | FALSE |
inflation_factor | FALSE |
n | TRUE |
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×N×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, ˆn.ratio_se_n
: ratio_se_n=√ˆn√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
: mean_diff=∑j^βstdj−βjn_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
: ratio_diff=|mean_diffmean_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
: r2=∑j2×β2j×MAFj×(1−MAFj)var1, var1=1.2
: r2=∑j2×β2j×MAFj×(1−MAFj)var2, var2=^sd1y2,3
: r2=∑j2×β2j×MAFj×(1−MAFj)var3, var3=^sd2y2,4
: r2=∑jFjFj+n−2, F=β2jse2j.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 χ2 statistics.ldsc_ratio
: ldsc_intercept_beta−1ldsc_mean_chisq−1, the proportion of the inflation in the mean χ2 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 h2 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 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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 | 0 | 1.0000000 | 3 | 58 | 0 | 10265275 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 97 | 0 | 38413 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 412 | 0 | 24018 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 10265284 | 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 | 8.643747e+00 | 5.756573e+00 | 1.000e+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 | 7.877894e+07 | 5.630825e+07 | 3.020e+02 | 3.256329e+07 | 6.917355e+07 | 1.143686e+08 | 2.492405e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -3.350000e-05 | 7.279170e-02 | -8.712e-01 | -3.000000e-02 | 0.000000e+00 | 3.000000e-02 | 9.145000e-01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 5.959380e-02 | 4.190010e-02 | 2.390e-02 | 2.810000e-02 | 4.050000e-02 | 7.890000e-02 | 2.523000e-01 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.977952e-01 | 2.890155e-01 | 4.000e-07 | 2.454709e-01 | 5.011872e-01 | 7.413102e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.977636e-01 | 2.889474e-01 | 4.000e-07 | 2.474250e-01 | 4.967504e-01 | 7.477664e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF | 277 | 0.9999730 | NA | NA | NA | NA | NA | NA | NA | 2.512646e-01 | 2.751608e-01 | 2.420e-03 | 2.907000e-02 | 1.321000e-01 | 4.053500e-01 | 9.988300e-01 | ▇▂▂▁▁ |
numeric | AF_reference | 477442 | 0.9534896 | NA | NA | NA | NA | NA | NA | NA | 2.332106e-01 | 2.519924e-01 | 0.000e+00 | 2.535940e-02 | 1.361820e-01 | 3.694090e-01 | 1.000000e+00 | ▇▂▂▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
1 | 10177 | rs367896724 | AC | A | -0.0262 | 0.0299 | 0.3801894 | 0.3808919 | 0.62806 | NA | NA |
1 | 10616 | rs376342519 | C | CCGCCGTTGCAAAGGCGCGCCG | -0.1938 | 0.1646 | 0.2398827 | 0.2390360 | 0.00751 | NA | NA |
1 | 11008 | rs575272151 | C | G | -0.0845 | 0.0518 | 0.1023291 | 0.1028325 | 0.08306 | 0.0880591 | NA |
1 | 13273 | rs531730856 | G | C | -0.0206 | 0.0434 | 0.6309573 | 0.6350333 | 0.13251 | 0.0950479 | NA |
1 | 13483 | rs554760071 | G | C | 0.1134 | 0.1959 | 0.5623413 | 0.5626791 | 0.00504 | 0.0019968 | NA |
1 | 14604 | rs541940975 | A | G | 0.0103 | 0.0370 | 0.7762471 | 0.7807219 | 0.18665 | 0.1475640 | NA |
1 | 14933 | rs199856693 | G | A | 0.0104 | 0.0677 | 0.8709640 | 0.8779102 | 0.04746 | 0.0283546 | NA |
1 | 18849 | rs533090414 | C | G | -0.1120 | 0.0796 | 0.1584890 | 0.1594170 | 0.96874 | 0.9518770 | NA |
1 | 30923 | rs806731 | G | T | -0.0385 | 0.0464 | 0.4073803 | 0.4066850 | 0.89387 | 0.8724040 | NA |
1 | 47159 | rs540662756 | T | C | -0.0190 | 0.0593 | 0.7413102 | 0.7486615 | 0.06190 | 0.0273562 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
22 | 51237063 | rs3896457 | T | C | -0.0323 | 0.0268 | 0.2290868 | 0.2281169 | 0.28870 | 0.2050720 | NA |
22 | 51237364 | rs200607599 | A | G | -0.0060 | 0.1161 | 0.9549930 | 0.9587840 | 0.01151 | 0.0187700 | NA |
22 | 51237712 | rs370652263 | G | A | 0.0234 | 0.0513 | 0.6456542 | 0.6482891 | 0.06180 | 0.0690895 | NA |
22 | 51238394 | rs149712012 | C | T | 0.0324 | 0.1834 | 0.8511380 | 0.8597731 | 0.00454 | 0.0033946 | NA |
22 | 51239281 | rs8138215 | G | C | -0.0558 | 0.2011 | 0.7762471 | 0.7814162 | 0.00379 | 0.0111821 | NA |
22 | 51239296 | rs8137179 | T | C | -0.0558 | 0.2011 | 0.7762471 | 0.7814162 | 0.00379 | 0.0111821 | NA |
22 | 51239304 | rs8142977 | C | T | -0.0558 | 0.2011 | 0.7762471 | 0.7814162 | 0.00379 | 0.0111821 | NA |
22 | 51239794 | rs561893765 | C | A | -0.3351 | 0.2140 | 0.1174900 | 0.1173749 | 0.00333 | 0.0299521 | NA |
22 | 51241386 | rs568168135 | C | G | -0.0948 | 0.1654 | 0.5623413 | 0.5665391 | 0.00560 | 0.0139776 | NA |
22 | 51244237 | rs575160859 | C | T | 0.0639 | 0.1168 | 0.5888437 | 0.5843176 | 0.01136 | 0.0037939 | NA |
1 10177 rs367896724 AC A . PASS AF=0.62806 ES:SE:LP:AF:ID -0.0262:0.0299:0.42:0.62806:rs367896724
1 10616 rs376342519 C CCGCCGTTGCAAAGGCGCGCCG . PASS AF=0.00751 ES:SE:LP:AF:ID -0.1938:0.1646:0.620001:0.00751:rs376342519
1 11008 rs575272151 C G . PASS AF=0.08306 ES:SE:LP:AF:ID -0.0845:0.0518:0.990001:0.08306:rs575272151
1 13273 rs531730856 G C . PASS AF=0.13251 ES:SE:LP:AF:ID -0.0206:0.0434:0.2:0.13251:rs531730856
1 13483 rs554760071 G C . PASS AF=0.00504 ES:SE:LP:AF:ID 0.1134:0.1959:0.25:0.00504:rs554760071
1 14604 rs541940975 A G . PASS AF=0.18665 ES:SE:LP:AF:ID 0.0103:0.037:0.11:0.18665:rs541940975
1 14933 rs199856693 G A . PASS AF=0.04746 ES:SE:LP:AF:ID 0.0104:0.0677:0.0599998:0.04746:rs199856693
1 18849 rs533090414 C G . PASS AF=0.96874 ES:SE:LP:AF:ID -0.112:0.0796:0.800001:0.96874:rs533090414
1 30923 rs806731 G T . PASS AF=0.89387 ES:SE:LP:AF:ID -0.0385:0.0464:0.39:0.89387:rs806731
1 47159 rs540662756 T C . PASS AF=0.0619 ES:SE:LP:AF:ID -0.019:0.0593:0.13:0.0619:rs540662756
1 49554 rs539322794 A G . PASS AF=0.08749 ES:SE:LP:AF:ID 0.0175:0.0524:0.13:0.08749:rs539322794
1 54712 rs568927205 TTTTC T . PASS AF=0.43775 ES:SE:LP:AF:ID -0.0415:0.0283:0.849999:0.43775:rs568927205
1 54945 rs569799965 C A . PASS AF=0.00751 ES:SE:LP:AF:ID 0.2029:0.1699:0.63:0.00751:rs569799965
1 55249 rs200769871 C CTATGG . PASS AF=0.01031 ES:SE:LP:AF:ID 0.3248:0.1419:1.66:0.01031:rs200769871
1 59040 rs62637815 T C . PASS AF=0.08548 ES:SE:LP:AF:ID 0.0112:0.0528:0.0799999:0.08548:rs62637815
1 60351 rs62637817 A G . PASS AF=0.08009 ES:SE:LP:AF:ID 0.0309:0.0542:0.25:0.08009:rs62637817
1 61208 rs527362206 T C . PASS AF=0.00728 ES:SE:LP:AF:ID 0.1712:0.1709:0.5:0.00728:rs527362206
1 61743 rs184286948 G C . PASS AF=0.00759 ES:SE:LP:AF:ID 0.2275:0.1685:0.75:0.00759:rs184286948
1 63093 rs200092917 G A . PASS AF=0.02888 ES:SE:LP:AF:ID 0.1072:0.0875:0.66:0.02888:rs200092917
1 63671 rs80011619 G A . PASS AF=0.15883 ES:SE:LP:AF:ID -0.0151:0.0399:0.15:0.15883:rs80011619
1 64649 rs181431124 A C . PASS AF=0.02531 ES:SE:LP:AF:ID 0.0197:0.0931:0.0799999:0.02531:rs181431124
1 64931 rs62639104 G A . PASS AF=0.07866 ES:SE:LP:AF:ID 0.0039:0.0543:0.0300001:0.07866:rs62639104
1 66219 rs181028663 A T . PASS AF=0.01917 ES:SE:LP:AF:ID -0.0403:0.1018:0.16:0.01917:rs181028663
1 67107 rs545950684 A G . PASS AF=0.00703 ES:SE:LP:AF:ID 0.2076:0.1733:0.64:0.00703:rs545950684
1 68082 rs367789441 T C . PASS AF=0.07119 ES:SE:LP:AF:ID 0.0346:0.0573:0.26:0.07119:rs367789441
1 69428 rs140739101 T G . PASS AF=0.03289 ES:SE:LP:AF:ID -0.0498:0.081:0.27:0.03289:rs140739101
1 69761 rs200505207 A T . PASS AF=0.07372 ES:SE:LP:AF:ID 0.0133:0.0566:0.0899997:0.07372:rs200505207
1 69897 rs200676709 T C . PASS AF=0.71804 ES:SE:LP:AF:ID -0.0088:0.0316:0.11:0.71804:rs200676709
1 77866 rs563593912 C T . PASS AF=0.0757 ES:SE:LP:AF:ID 0.0289:0.0548:0.22:0.0757:rs563593912
1 81587 rs536406113 C T . PASS AF=0.06385 ES:SE:LP:AF:ID 0.0936:0.0597:0.929999:0.06385:rs536406113
1 82163 rs139113303 G A . PASS AF=0.07738 ES:SE:LP:AF:ID 0.0217:0.0529:0.17:0.07738:rs139113303
1 82609 rs149189449 C G . PASS AF=0.07539 ES:SE:LP:AF:ID 0.0266:0.0537:0.21:0.07539:rs149189449
1 86065 rs116504101 G C . PASS AF=0.0764 ES:SE:LP:AF:ID 0.0432:0.0536:0.38:0.0764:rs116504101
1 87409 rs139490478 C T . PASS AF=0.07661 ES:SE:LP:AF:ID 0.0423:0.0535:0.369999:0.07661:rs139490478
1 88169 rs940550 C T . PASS AF=0.20467 ES:SE:LP:AF:ID -0.0126:0.0361:0.14:0.20467:rs940550
1 88172 rs940551 G A . PASS AF=0.07528 ES:SE:LP:AF:ID 0.046:0.0553:0.39:0.07528:rs940551
1 88177 rs143215837 G C . PASS AF=0.07235 ES:SE:LP:AF:ID 0.0374:0.0564:0.3:0.07235:rs143215837
1 88316 rs113759966 G A . PASS AF=0.07124 ES:SE:LP:AF:ID 0.0327:0.0571:0.25:0.07124:rs113759966
1 88338 rs55700207 G A . PASS AF=0.07793 ES:SE:LP:AF:ID 0.0132:0.0534:0.0899997:0.07793:rs55700207
1 88710 rs186575039 C G . PASS AF=0.07789 ES:SE:LP:AF:ID 0.0254:0.053:0.2:0.07789:rs186575039
1 89599 rs375955515 A T . PASS AF=0.07642 ES:SE:LP:AF:ID 0.035:0.0532:0.29:0.07642:rs375955515
1 91190 rs143856811 G A . PASS AF=0.08117 ES:SE:LP:AF:ID 0.0379:0.0517:0.33:0.08117:rs143856811
1 91340 rs376250562 C G . PASS AF=0.01521 ES:SE:LP:AF:ID 0.0389:0.1198:0.13:0.01521:rs376250562
1 91358 rs370712517 G T . PASS AF=0.01478 ES:SE:LP:AF:ID 0.0694:0.1208:0.25:0.01478:rs370712517
1 91421 rs28619159 T C . PASS AF=0.01861 ES:SE:LP:AF:ID 0.1453:0.1034:0.800001:0.01861:rs28619159
1 91515 rs376723915 A C . PASS AF=0.54508 ES:SE:LP:AF:ID -0.0379:0.029:0.72:0.54508:rs376723915
1 91536 rs6702460 G T . PASS AF=0.56854 ES:SE:LP:AF:ID -0.0401:0.0291:0.779999:0.56854:rs6702460
1 92858 rs147061536 G T . PASS AF=0.22951 ES:SE:LP:AF:ID 0.0078:0.0348:0.0899997:0.22951:rs147061536
1 99687 rs139153227 C T . PASS AF=0.06852 ES:SE:LP:AF:ID 0.0097:0.0578:0.0599998:0.06852:rs139153227
1 104281 rs576842010 T C . PASS AF=0.04001 ES:SE:LP:AF:ID -0.0904:0.0748:0.64:0.04001:rs576842010