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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/166e95f2-042c-409c-9c8c-b89d4181f2df/call-vcf/inputs/-261044565/upload.txt.gz --id ieu-b-4809 --json /data/cromwell-executions/qc/166e95f2-042c-409c-9c8c-b89d4181f2df/call-vcf/inputs/-261044565/ieu-b-4809_data.json --ref /data/cromwell-executions/qc/166e95f2-042c-409c-9c8c-b89d4181f2df/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/166e95f2-042c-409c-9c8c-b89d4181f2df/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-4809/ieu-b-4809.vcf.gz --alias alias.txt --cohort_cases 9132 --cohort_controls 173493; 1.3.0",
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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 /data/cromwell-executions/qc/166e95f2-042c-409c-9c8c-b89d4181f2df/call-ldsc/inputs/-261044565/ieu-b-4809.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4809/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Thu Dec 16 19:52:34 2021
Reading summary statistics from /data/cromwell-executions/qc/166e95f2-042c-409c-9c8c-b89d4181f2df/call-ldsc/inputs/-261044565/ieu-b-4809.vcf.gz ...
Read summary statistics for 12096462 SNPs.
Dropped 202555 SNPs with duplicated rs numbers.
Reading reference panel LD Score from /data/ref/eur_w_ld_chr/[1-22] ... (ldscore_fromlist)
Read reference panel LD Scores for 1290028 SNPs.
Removing partitioned LD Scores with zero variance.
Reading regression weight LD Score from /data/ref/eur_w_ld_chr/[1-22] ... (ldscore_fromlist)
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1220144 SNPs remain.
After merging with regression SNP LD, 1220144 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0431 (0.0043)
Lambda GC: 1.1129
Mean Chi^2: 1.1721
Intercept: 1.0218 (0.0078)
Ratio: 0.1265 (0.0454)
Analysis finished at Thu Dec 16 19:54:38 2021
Total time elapsed: 2.0m:4.07s
{
"af_correlation": 0.9498,
"inflation_factor": 1.0966,
"mean_EFFECT": -3.2959e-06,
"n": "-Inf",
"n_snps": 12097504,
"n_clumped_hits": 39,
"n_p_sig": 3453,
"n_mono": 0,
"n_ns": 1283818,
"n_mac": 0,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 0,
"n_miss_AF_reference": 1376536,
"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": 1220144,
"ldsc_nsnp_merge_regression_ld": 1220144,
"ldsc_observed_scale_h2_beta": 0.0431,
"ldsc_observed_scale_h2_se": 0.0043,
"ldsc_intercept_beta": 1.0218,
"ldsc_intercept_se": 0.0078,
"ldsc_lambda_gc": 1.1129,
"ldsc_mean_chisq": 1.1721,
"ldsc_ratio": 0.1267
}
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 | 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 | logical.mean | logical.count | numeric.mean | numeric.sd | numeric.p0 | numeric.p25 | numeric.p50 | numeric.p75 | numeric.p100 | numeric.hist |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
character | ID | 674 | 0.9999443 | 3 | 58 | 0 | 12053925 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 88 | 0 | 17422 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 662 | 0 | 71134 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 12097504 | 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 | 8.764304e+00 | 5.889801e+00 | 1.0000000 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.300000e+01 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 7.868374e+07 | 5.624302e+07 | 302.0000000 | 3.248884e+07 | 6.922840e+07 | 1.144345e+08 | 2.492405e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -3.300000e-06 | 3.035800e-03 | -0.1323800 | -1.021900e-03 | -1.350000e-05 | 9.867000e-04 | 1.406710e-01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.233900e-03 | 2.000600e-03 | 0.0005095 | 8.330000e-04 | 1.312400e-03 | 2.949800e-03 | 3.663960e-02 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.871216e-01 | 2.928479e-01 | 0.0000000 | 2.300001e-01 | 4.799997e-01 | 7.400005e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.871226e-01 | 2.928214e-01 | 0.0000000 | 2.303792e-01 | 4.836845e-01 | 7.406559e-01 | 9.999999e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.629684e-01 | 3.018262e-01 | 0.0013690 | 1.835900e-02 | 1.206230e-01 | 4.442520e-01 | 9.986310e-01 | ▇▂▂▁▁ |
numeric | AF_reference | 1376536 | 0.8862132 | NA | NA | NA | NA | NA | NA | NA | 2.159485e-01 | 2.516945e-01 | 0.0000000 | 1.317890e-02 | 1.096250e-01 | 3.426520e-01 | 1.000000e+00 | ▇▂▁▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 10177 | rs1264289758 | AC | A | -0.0014889 | 0.0010762 | 0.1700000 | 0.1665185 | 0.600633 | NA | NA |
1 | 10352 | rs1557426776 | TA | T | -0.0017392 | 0.0011092 | 0.1199999 | 0.1168940 | 0.607088 | NA | NA |
1 | 11008 | rs575272151 | C | G | 0.0035340 | 0.0018344 | 0.0539995 | 0.0540315 | 0.086716 | 0.0880591 | NA |
1 | 11012 | rs544419019 | C | G | 0.0035340 | 0.0018344 | 0.0539995 | 0.0540315 | 0.086716 | 0.0880591 | NA |
1 | 13110 | rs540538026 | G | A | 0.0037501 | 0.0024454 | 0.1299999 | 0.1251494 | 0.058961 | 0.0267572 | NA |
1 | 13116 | rs62635286 | T | G | 0.0002115 | 0.0014509 | 0.8800001 | 0.8841237 | 0.189513 | 0.0970447 | NA |
1 | 13118 | rs200579949 | A | G | 0.0002115 | 0.0014509 | 0.8800001 | 0.8841237 | 0.189513 | 0.0970447 | NA |
1 | 13273 | rs531730856 | G | C | 0.0002035 | 0.0017024 | 0.9000000 | 0.9048628 | 0.134078 | 0.0950479 | NA |
1 | 14464 | rs546169444 | A | T | -0.0020263 | 0.0015488 | 0.1900002 | 0.1907747 | 0.156680 | 0.0958466 | NA |
1 | 14599 | rs531646671 | T | A | 0.0028568 | 0.0014059 | 0.0420001 | 0.0421558 | 0.192148 | 0.1475640 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
23 | 154901936 | rs697727 | A | G | 0.0012525 | 0.0005901 | 0.0340001 | 0.0337834 | 0.752169 | 0.643179 | NA |
23 | 154901964 | rs697726 | G | A | 0.0008790 | 0.0006218 | 0.1600000 | 0.1574538 | 0.348234 | 0.117616 | NA |
23 | 154902105 | rs696316 | G | T | 0.0012545 | 0.0005900 | 0.0329997 | 0.0334905 | 0.752149 | 0.636026 | NA |
23 | 154902889 | rs697725 | A | T | 0.0012348 | 0.0005898 | 0.0359998 | 0.0363112 | 0.751853 | 0.584106 | NA |
23 | 154903118 | rs479770 | G | A | 0.0012624 | 0.0005901 | 0.0320000 | 0.0324067 | 0.752202 | 0.643444 | NA |
23 | 154903224 | rs480725 | A | T | 0.0012624 | 0.0005901 | 0.0320000 | 0.0324152 | 0.752203 | 0.643444 | NA |
23 | 154903937 | rs674707 | G | A | 0.0012615 | 0.0005901 | 0.0329997 | 0.0325369 | 0.752209 | 0.643444 | NA |
23 | 154909055 | rs473529 | C | G | -0.0011323 | 0.0005555 | 0.0420001 | 0.0414994 | 0.303988 | 0.463046 | NA |
23 | 154918266 | rs642043 | C | T | -0.0012232 | 0.0005572 | 0.0280001 | 0.0281485 | 0.301862 | 0.478675 | NA |
23 | 154927581 | rs644138 | G | A | -0.0012364 | 0.0005573 | 0.0269998 | 0.0265262 | 0.301754 | 0.463576 | NA |
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