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"gwas_harmonisation_command": "--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/vcf_09_19b/bgzip_vcf/data.batch_41229_5N4.vcf.gz --id UKB-b:18381 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_41229_5N4.txt.gz --cohort_cases 6927 --cohort_controls 456083 --ref /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/human_g1k_v37.fasta --json /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/ukb_gwas.json; 1.1.1",
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"bcftools_viewCommand.1": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-b-18381/ukb-b-18381.vcf.gz; Date=Sun May 10 14:54:40 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/public/UKB-b-18381/UKB-b-18381_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-18381/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:40:18 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-18381/UKB-b-18381_data.vcf.gz ...
Read summary statistics for 5412581 SNPs.
Dropped 1915 SNPs with duplicated rs numbers.
Reading reference panel LD Score from ../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 ../reference/eur_w_ld_chr/[1-22] ...
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1164329 SNPs remain.
After merging with regression SNP LD, 1164329 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0025 (0.0015)
Lambda GC: 1.2753
Mean Chi^2: 1.2797
Intercept: 1.2556 (0.0092)
Ratio: 0.9141 (0.0331)
Analysis finished at Thu Oct 17 14:41:21 2019
Total time elapsed: 1.0m:3.65s
{
"af_correlation": 0.915,
"inflation_factor": 1.2544,
"mean_EFFECT": 6.2227e-07,
"n": "-Inf",
"n_snps": 9851866,
"n_clumped_hits": 2,
"n_p_sig": 2,
"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": 47202,
"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": 1164329,
"ldsc_nsnp_merge_regression_ld": 1164329,
"ldsc_observed_scale_h2_beta": 0.0025,
"ldsc_observed_scale_h2_se": 0.0015,
"ldsc_intercept_beta": 1.2556,
"ldsc_intercept_se": 0.0092,
"ldsc_lambda_gc": 1.2753,
"ldsc_mean_chisq": 1.2797,
"ldsc_ratio": 0.9138
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | TRUE |
n | TRUE |
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 | TRUE |
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 | 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 | 5410681 | 0 | NA | NA | 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 | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 5412581 | 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 | 8.672642e+00 | 5.763511e+00 | 1.0000000 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 7.854995e+07 | 5.656768e+07 | 828.0000000 | 3.194258e+07 | 6.896544e+07 | 1.144980e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 6.000000e-07 | 3.966000e-04 | -0.0029771 | -2.468000e-04 | -1.000000e-07 | 2.470000e-04 | 3.163100e-03 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 3.394000e-04 | 9.050000e-05 | 0.0002414 | 2.636000e-04 | 3.058000e-04 | 3.948000e-04 | 1.140900e-03 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.603633e-01 | 2.978115e-01 | 0.0000000 | 1.900002e-01 | 4.500005e-01 | 7.199992e-01 | 1.000000e+00 | ▇▆▆▅▆ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.603630e-01 | 2.977867e-01 | 0.0000000 | 1.920806e-01 | 4.456633e-01 | 7.172767e-01 | 9.999994e-01 | ▇▆▆▆▆ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 3.348599e-01 | 2.457366e-01 | 0.0505270 | 1.245290e-01 | 2.625400e-01 | 5.016960e-01 | 9.494730e-01 | ▇▃▂▂▂ |
numeric | AF_reference | 47202 | 0.9912792 | NA | NA | NA | NA | NA | NA | NA | 3.297102e-01 | 2.406034e-01 | 0.0000000 | 1.315890e-01 | 2.667730e-01 | 4.914140e-01 | 1.000000e+00 | ▇▆▃▂▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | 0.0003029 | 0.0004438 | 0.4899999 | 0.4949450 | 0.623765 | 0.7821490 | NA |
1 | 54676 | rs2462492 | C | T | 0.0002021 | 0.0004397 | 0.6499995 | 0.6457356 | 0.400401 | NA | NA |
1 | 86028 | rs114608975 | T | C | -0.0003773 | 0.0007029 | 0.5900000 | 0.5914198 | 0.103556 | 0.0277556 | NA |
1 | 91536 | rs6702460 | G | T | -0.0004885 | 0.0004329 | 0.2599998 | 0.2590888 | 0.456846 | 0.4207270 | NA |
1 | 234313 | rs8179466 | C | T | -0.0011323 | 0.0008536 | 0.1800002 | 0.1846659 | 0.074506 | NA | NA |
1 | 534192 | rs6680723 | C | T | 0.0003962 | 0.0004945 | 0.4199997 | 0.4229889 | 0.240959 | NA | NA |
1 | 546697 | rs12025928 | A | G | 0.0006123 | 0.0006169 | 0.3200000 | 0.3209461 | 0.913475 | NA | NA |
1 | 693731 | rs12238997 | A | G | 0.0004820 | 0.0004144 | 0.2399999 | 0.2448031 | 0.116329 | 0.1417730 | NA |
1 | 705882 | rs72631875 | G | A | -0.0003727 | 0.0006072 | 0.5400003 | 0.5393443 | 0.067288 | 0.0315495 | NA |
1 | 706368 | rs55727773 | A | G | -0.0000686 | 0.0003070 | 0.8200001 | 0.8231712 | 0.515645 | 0.2751600 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51217954 | rs9616974 | G | A | -0.0006679 | 0.0004806 | 0.1600000 | 0.1646657 | 0.073312 | 0.0621006 | NA |
22 | 51218224 | rs9616975 | C | A | -0.0006748 | 0.0004808 | 0.1600000 | 0.1605062 | 0.073333 | 0.0619010 | NA |
22 | 51218377 | rs2519461 | G | C | -0.0006554 | 0.0004803 | 0.1700000 | 0.1723615 | 0.073622 | 0.0826677 | NA |
22 | 51219006 | rs28729663 | G | A | -0.0004890 | 0.0003707 | 0.1900002 | 0.1871915 | 0.137950 | 0.2052720 | NA |
22 | 51219387 | rs9616832 | T | C | -0.0006692 | 0.0004812 | 0.1600000 | 0.1643614 | 0.073744 | 0.0654952 | NA |
22 | 51221731 | rs115055839 | T | C | -0.0006905 | 0.0004815 | 0.1499999 | 0.1515675 | 0.073235 | 0.0625000 | NA |
22 | 51222100 | rs114553188 | G | T | -0.0000587 | 0.0005669 | 0.9199999 | 0.9175391 | 0.054460 | 0.0880591 | NA |
22 | 51223637 | rs375798137 | G | A | -0.0000530 | 0.0005696 | 0.9299999 | 0.9258555 | 0.054089 | 0.0788738 | NA |
22 | 51229805 | rs9616985 | T | C | -0.0007367 | 0.0004833 | 0.1299999 | 0.1273891 | 0.073071 | 0.0730831 | NA |
22 | 51237063 | rs3896457 | T | C | 0.0004881 | 0.0002956 | 0.0990011 | 0.0986414 | 0.297974 | 0.2050720 | NA |
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