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"gwas_harmonisation_command": "--json /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-379/ukb-a-379_data.json --ref /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/QC/genomes/b37/human_g1k_v37.fasta; 1.1.1",
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"bcftools_annotateCommand": "annotate -a /mnt/storage/home/gh13047/mr-eve/vcf-reference-datasets/dbsnp/dbsnp.v153.b37.vcf.gz -c ID -o /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-379/ukb-a-379.vcf.gz -O z /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-379/ukb-a-379_data.vcf.gz; Date=Sun Feb 16 01:28:41 2020",
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"bcftools_viewCommand": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-a-379/ukb-a-379.vcf.gz; Date=Sat May 9 20:21:56 2020"
}
*********************************************************************
* 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-379/ukb-a-379.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-379/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 01:56:37 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-379/ukb-a-379.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: 0.1009 (0.0036)
Lambda GC: 1.5449
Mean Chi^2: 1.7302
Intercept: 1.0664 (0.01)
Ratio: 0.0909 (0.0137)
Analysis finished at Sun Feb 16 01:58:21 2020
Total time elapsed: 1.0m:44.28s
{
"af_correlation": 0.9533,
"inflation_factor": 1.3263,
"mean_EFFECT": -0,
"n": 335842,
"n_snps": 10877936,
"n_clumped_hits": 104,
"n_p_sig": 9546,
"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": 334350.5088,
"ratio_se_n": 0.9978,
"mean_diff": -0,
"ratio_diff": 8.4142,
"sd_y_est1": 0.7234,
"sd_y_est2": 0.7218,
"r2_sum1": 0.0073,
"r2_sum2": 0.0139,
"r2_sum3": 0.014,
"r2_sum4": 0.014,
"ldsc_nsnp_merge_refpanel_ld": 1281483,
"ldsc_nsnp_merge_regression_ld": 1281483,
"ldsc_observed_scale_h2_beta": 0.1009,
"ldsc_observed_scale_h2_se": 0.0036,
"ldsc_intercept_beta": 1.0664,
"ldsc_intercept_se": 0.01,
"ldsc_lambda_gc": 1.5449,
"ldsc_mean_chisq": 1.7302,
"ldsc_ratio": 0.0909
}
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 | -4.720000e-05 | 1.092040e-02 | -1.39207e-01 | -3.390000e-03 | -1.170000e-05 | 3.343200e-03 | 1.269460e-01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.602500e-03 | 7.200500e-03 | 1.74420e-03 | 2.154200e-03 | 4.137500e-03 | 1.105580e-02 | 3.955280e-02 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.539449e-01 | 3.009761e-01 | 0.00000e+00 | 1.819730e-01 | 4.372844e-01 | 7.146757e-01 | 1.000000e+00 | ▇▆▆▅▅ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.539445e-01 | 3.009763e-01 | 0.00000e+00 | 1.819719e-01 | 4.372835e-01 | 7.146742e-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 | 3.358420e+05 | 0.000000e+00 | 3.35842e+05 | 3.358420e+05 | 3.358420e+05 | 3.358420e+05 | 3.358420e+05 | ▁▁▇▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 693731 | rs12238997 | A | G | -0.0040156 | 0.0029118 | 0.1678711 | 0.1678694 | 0.1169260 | 0.1417730 | 335842 |
1 | 717587 | rs144155419 | G | A | 0.0053380 | 0.0078210 | 0.4949097 | 0.4949096 | 0.0143862 | 0.0045926 | 335842 |
1 | 730087 | rs148120343 | T | C | -0.0039874 | 0.0040577 | 0.3257639 | 0.3257638 | 0.0554733 | 0.0127796 | 335842 |
1 | 731718 | rs142557973 | T | C | -0.0036805 | 0.0027624 | 0.1827469 | 0.1827464 | 0.1216580 | 0.1543530 | 335842 |
1 | 734349 | rs141242758 | T | C | -0.0036310 | 0.0027640 | 0.1889601 | 0.1889593 | 0.1215130 | 0.1525560 | 335842 |
1 | 740284 | rs61770167 | C | T | -0.0047252 | 0.0125909 | 0.7074455 | 0.7074453 | 0.0058556 | 0.0023962 | 335842 |
1 | 742813 | rs112573343 | C | T | 0.0017881 | 0.0236995 | 0.9398560 | 0.9398563 | 0.0015525 | 0.1030350 | 335842 |
1 | 753405 | rs3115860 | C | A | 0.0032511 | 0.0026262 | 0.2157228 | 0.2157222 | 0.8706760 | 0.7517970 | 335842 |
1 | 753541 | rs2073813 | G | A | -0.0031160 | 0.0026328 | 0.2365860 | 0.2365854 | 0.1288330 | 0.3019170 | 335842 |
1 | 754182 | rs3131969 | A | G | 0.0031779 | 0.0026234 | 0.2257538 | 0.2257524 | 0.8703180 | 0.6785140 | 335842 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219387 | rs9616832 | T | C | -0.0010725 | 0.0033824 | 0.7511782 | 0.7511778 | 0.0729806 | 0.0654952 | 335842 |
22 | 51219704 | rs147475742 | G | A | -0.0033150 | 0.0045338 | 0.4646715 | 0.4646708 | 0.0418225 | 0.0473243 | 335842 |
22 | 51219766 | rs182321900 | C | T | -0.0243271 | 0.0233946 | 0.2984070 | 0.2984051 | 0.0014546 | NA | 335842 |
22 | 51220088 | rs566371895 | G | A | -0.0086482 | 0.0152386 | 0.5703625 | 0.5703623 | 0.0039843 | 0.0003994 | 335842 |
22 | 51220146 | rs868950473 | C | T | -0.0164020 | 0.0230410 | 0.4765517 | 0.4765506 | 0.0015139 | NA | 335842 |
22 | 51221731 | rs115055839 | T | C | -0.0011968 | 0.0033845 | 0.7236257 | 0.7236246 | 0.0728101 | 0.0625000 | 335842 |
22 | 51223637 | rs375798137 | G | A | 0.0044879 | 0.0039864 | 0.2602520 | 0.2602512 | 0.0540289 | 0.0788738 | 335842 |
22 | 51226692 | rs150189434 | G | A | -0.0259368 | 0.0238917 | 0.2776572 | 0.2776565 | 0.0013983 | 0.0155751 | 335842 |
22 | 51229805 | rs9616985 | T | C | -0.0012724 | 0.0033973 | 0.7080208 | 0.7080198 | 0.0727671 | 0.0730831 | 335842 |
22 | 51237063 | rs3896457 | T | C | 0.0006334 | 0.0020674 | 0.7593308 | 0.7593305 | 0.2968410 | 0.2050720 | 335842 |
1 693731 rs12238997 A G . PASS AF=0.116926 ES:SE:LP:AF:SS:ID -0.00401557:0.00291177:0.775024:0.116926:335842:rs12238997
1 717587 rs144155419 G A . PASS AF=0.0143862 ES:SE:LP:AF:SS:ID 0.00533799:0.00782099:0.305474:0.0143862:335842:rs144155419
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1 731718 rs58276399 T C . PASS AF=0.121658 ES:SE:LP:AF:SS:ID -0.00368054:0.00276245:0.73815:0.121658:335842:rs58276399
1 734349 rs141242758 T C . PASS AF=0.121513 ES:SE:LP:AF:SS:ID -0.00363102:0.00276404:0.72363:0.121513:335842:rs141242758
1 740284 rs61770167 C T . PASS AF=0.00585559 ES:SE:LP:AF:SS:ID -0.00472523:0.0125909:0.150307:0.00585559:335842:rs61770167
1 742813 rs112573343 C T . PASS AF=0.0015525 ES:SE:LP:AF:SS:ID 0.00178814:0.0236995:0.0269387:0.0015525:335842:rs112573343
1 753405 rs3115860 C A . PASS AF=0.870676 ES:SE:LP:AF:SS:ID 0.00325113:0.00262615:0.666104:0.870676:335842:rs3115860
1 753541 rs2073813 G A . PASS AF=0.128833 ES:SE:LP:AF:SS:ID -0.00311603:0.00263275:0.626011:0.128833:335842:rs2073813
1 754182 rs3131969 A G . PASS AF=0.870318 ES:SE:LP:AF:SS:ID 0.00317788:0.00262337:0.646365:0.870318:335842:rs3131969
1 754192 rs3131968 A G . PASS AF=0.870409 ES:SE:LP:AF:SS:ID 0.00309771:0.0026246:0.623607:0.870409:335842:rs3131968
1 754334 rs3131967 T C . PASS AF=0.870037 ES:SE:LP:AF:SS:ID 0.00323093:0.00262327:0.661376:0.870037:335842:rs3131967
1 754433 rs150578204 G A . PASS AF=0.00465304 ES:SE:LP:AF:SS:ID 0.0066422:0.0133884:0.20774:0.00465304:335842:rs150578204
1 754458 rs142682604 G T . PASS AF=0.00464711 ES:SE:LP:AF:SS:ID 0.0068634:0.0134247:0.215257:0.00464711:335842:rs142682604
1 755435 rs184270342 T G . PASS AF=0.00590897 ES:SE:LP:AF:SS:ID -0.00516449:0.0130616:0.159548:0.00590897:335842:rs184270342
1 755890 rs3115858 A T . PASS AF=0.870329 ES:SE:LP:AF:SS:ID 0.0032394:0.00261874:0.665375:0.870329:335842:rs3115858
1 756604 rs3131962 A G . PASS AF=0.87002 ES:SE:LP:AF:SS:ID 0.00341397:0.00261247:0.718326:0.87002:335842:rs3131962
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1 758144 rs3131956 A G . PASS AF=0.870222 ES:SE:LP:AF:SS:ID 0.00331722:0.0026149:0.689116:0.870222:335842:rs3131956
1 758626 rs3131954 C T . PASS AF=0.870396 ES:SE:LP:AF:SS:ID 0.00339732:0.0026216:0.709939:0.870396:335842:rs3131954
1 761732 rs2286139 C T . PASS AF=0.867743 ES:SE:LP:AF:SS:ID 0.00376807:0.00260908:0.82775:0.867743:335842:rs2286139
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1 768819 rs12562811 C T . PASS AF=0.00692766 ES:SE:LP:AF:SS:ID -0.022129:0.0106238:1.4288:0.00692766:335842:rs12562811
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1 770377 rs112563271 A T . PASS AF=0.00692321 ES:SE:LP:AF:SS:ID -0.0219682:0.0106699:1.40334:0.00692321:335842:rs112563271
1 771823 rs2977605 T C . PASS AF=0.869934 ES:SE:LP:AF:SS:ID 0.00358643:0.00261715:0.76808:0.869934:335842:rs2977605
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1 772755 rs2905039 A C . PASS AF=0.870112 ES:SE:LP:AF:SS:ID 0.00358465:0.00261728:0.767489:0.870112:335842:rs2905039
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1 776556 rs151160018 C T . PASS AF=0.00851871 ES:SE:LP:AF:SS:ID -0.0126941:0.00981514:0.707963:0.00851871:335842:rs151160018
1 777122 rs2980319 A T . PASS AF=0.871122 ES:SE:LP:AF:SS:ID 0.00371154:0.00262165:0.804496:0.871122:335842:rs2980319
1 777232 rs112618790 C T . PASS AF=0.0961319 ES:SE:LP:AF:SS:ID -0.00168272:0.00302636:0.237924:0.0961319:335842:rs112618790
1 778745 rs1055606 A G . PASS AF=0.127871 ES:SE:LP:AF:SS:ID -0.00377744:0.0026303:0.821118:0.127871:335842:rs1055606
1 779322 rs4040617 A G . PASS AF=0.127984 ES:SE:LP:AF:SS:ID -0.00382042:0.00262674:0.836165:0.127984:335842:rs4040617
1 780785 rs2977612 T A . PASS AF=0.870455 ES:SE:LP:AF:SS:ID 0.0034282:0.00261733:0.72065:0.870455:335842:rs2977612
1 781367 rs149821290 A C . PASS AF=0.00989772 ES:SE:LP:AF:SS:ID -0.00324157:0.0093144:0.137971:0.00989772:335842:rs149821290
1 781845 rs61768199 A G . PASS AF=0.1044 ES:SE:LP:AF:SS:ID -0.00633871:0.0029434:1.50477:0.1044:335842:rs61768199
1 782721 rs185280546 G A . PASS AF=0.0143713 ES:SE:LP:AF:SS:ID 0.0171789:0.00796757:1.50757:0.0143713:335842:rs185280546
1 782981 rs6594026 C T . PASS AF=0.128338 ES:SE:LP:AF:SS:ID -0.00346319:0.00262816:0.726776:0.128338:335842:rs6594026
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1 783194 rs138555831 G T . PASS AF=0.0143713 ES:SE:LP:AF:SS:ID 0.0189032:0.00800024:1.74145:0.0143713:335842:rs138555831
1 783711 rs184266993 G A . PASS AF=0.00541372 ES:SE:LP:AF:SS:ID 0.000996084:0.0127838:0.0278462:0.00541372:335842:rs184266993
1 785050 rs2905062 G A . PASS AF=0.87014 ES:SE:LP:AF:SS:ID 0.00334938:0.00261773:0.697403:0.87014:335842:rs2905062
1 785989 rs2980300 T C . PASS AF=0.87009 ES:SE:LP:AF:SS:ID 0.00335243:0.00261939:0.697676:0.87009:335842:rs2980300