manhattan_plot
qq_plot
af_plot
pz_plot
beta_std_plot
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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/86a68996-12f5-43f8-bffa-e2b681f7cafe/call-vcf/inputs/-261021448/upload.txt.gz --id ieu-b-5120 --json /data/cromwell-executions/qc/86a68996-12f5-43f8-bffa-e2b681f7cafe/call-vcf/inputs/-261021448/ieu-b-5120_data.json --ref /data/cromwell-executions/qc/86a68996-12f5-43f8-bffa-e2b681f7cafe/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/86a68996-12f5-43f8-bffa-e2b681f7cafe/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-5120/ieu-b-5120.vcf.gz --alias alias.txt; 1.3.0",
"file_date": "2024-01-20T16:24:32.346036",
"bcftools_viewVersion": "1.9+htslib-1.9",
"bcftools_viewCommand": "view -h /data/cromwell-executions/qc/86a68996-12f5-43f8-bffa-e2b681f7cafe/call-report/inputs/-261021448/ieu-b-5120.vcf.gz; Date=Sat Jan 20 16:54:08 2024"
}
*********************************************************************
* 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/86a68996-12f5-43f8-bffa-e2b681f7cafe/call-ldsc/inputs/-261021448/ieu-b-5120.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-5120/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Sat Jan 20 16:43:00 2024
Reading summary statistics from /data/cromwell-executions/qc/86a68996-12f5-43f8-bffa-e2b681f7cafe/call-ldsc/inputs/-261021448/ieu-b-5120.vcf.gz ...
Read summary statistics for 0 SNPs.
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.
Traceback (most recent call last):
File "./ldsc/ldsc.py", line 647, in <module>
sumstats.estimate_h2(args, log)
File "/ldsc/ldscore/sumstats.py", line 330, in estimate_h2
args, log, args.h2)
File "/ldsc/ldscore/sumstats.py", line 252, in _read_ld_sumstats
sumstats = _merge_and_log(ref_ld, sumstats, 'reference panel LD', log)
File "/ldsc/ldscore/sumstats.py", line 238, in _merge_and_log
raise ValueError(msg.format(N=len(sumstats), F=noun))
ValueError: After merging with reference panel LD, 0 SNPs remain.
Analysis finished at Sat Jan 20 16:44:16 2024
Total time elapsed: 1.0m:15.82s
{
"af_correlation": 0.9506,
"inflation_factor": 1.0475,
"mean_EFFECT": 0.0013,
"n": "-Inf",
"n_snps": 11469218,
"n_clumped_hits": 4,
"n_p_sig": 194,
"n_mono": 0,
"n_ns": 529292,
"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": 693417,
"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": 0,
"ldsc_nsnp_merge_regression_ld": "NA",
"ldsc_observed_scale_h2_beta": "NA",
"ldsc_observed_scale_h2_se": "NA",
"ldsc_intercept_beta": "NA",
"ldsc_intercept_se": "NA",
"ldsc_lambda_gc": "NA",
"ldsc_mean_chisq": "NA",
"ldsc_ratio": "NA"
}
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 | NA |
n_p_sig | FALSE |
miss_EFFECT | FALSE |
miss_SE | FALSE |
miss_PVAL | FALSE |
ldsc_ratio | NA |
ldsc_intercept_beta | NA |
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 | 586 | 0.9999489 | 3 | 58 | 0 | 11443864 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 4 | 0 | 340 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 4 | 0 | 340 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 11469218 | 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 | 8.630471e+00 | 5.755513e+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 | 7.864496e+07 | 5.630108e+07 | 302.0000000 | 3.246429e+07 | 6.907161e+07 | 1.143027e+08 | 2.492405e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.255000e-03 | 2.655216e-01 | -4.2854100 | -7.851240e-02 | 8.013000e-04 | 8.056630e-02 | 4.239160e+00 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.906384e-01 | 1.836282e-01 | 0.0540247 | 6.578190e-02 | 1.075750e-01 | 2.489280e-01 | 2.850830e+00 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.927492e-01 | 2.902914e-01 | 0.0000000 | 2.399999e-01 | 4.899999e-01 | 7.400005e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.927499e-01 | 2.902678e-01 | 0.0000000 | 2.396809e-01 | 4.902065e-01 | 7.438615e-01 | 9.999999e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.258798e-01 | 2.758327e-01 | 0.0004370 | 1.447300e-02 | 9.182500e-02 | 3.638730e-01 | 9.994900e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 693417 | 0.9395410 | NA | NA | NA | NA | NA | NA | NA | 2.098983e-01 | 2.494755e-01 | 0.0000000 | 1.178120e-02 | 1.028350e-01 | 3.296730e-01 | 1.000000e+00 | ▇▂▁▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 10177 | rs1264289758 | AC | A | -0.0884710 | 0.0838036 | 0.2900000 | 0.2911078 | 0.599372 | NA | NA |
1 | 10352 | rs1557426776 | TA | T | 0.0515122 | 0.0861089 | 0.5500004 | 0.5496921 | 0.605168 | NA | NA |
1 | 11008 | rs575272151 | C | G | 0.0099795 | 0.1446500 | 0.9400001 | 0.9449972 | 0.085849 | 0.0880591 | NA |
1 | 11012 | rs544419019 | C | G | 0.0099795 | 0.1446500 | 0.9400001 | 0.9449972 | 0.085849 | 0.0880591 | NA |
1 | 13110 | rs540538026 | G | A | -0.0131814 | 0.1932380 | 0.9500000 | 0.9456158 | 0.057902 | 0.0267572 | NA |
1 | 13116 | rs62635286 | T | G | -0.0932537 | 0.1132970 | 0.4100001 | 0.4104565 | 0.188683 | 0.0970447 | NA |
1 | 13118 | rs200579949 | A | G | -0.0932537 | 0.1132970 | 0.4100001 | 0.4104565 | 0.188683 | 0.0970447 | NA |
1 | 13273 | rs531730856 | G | C | 0.0188337 | 0.1313450 | 0.8900000 | 0.8859813 | 0.134780 | 0.0950479 | NA |
1 | 14464 | rs546169444 | A | T | 0.0664099 | 0.1182890 | 0.5700002 | 0.5745107 | 0.158811 | 0.0958466 | NA |
1 | 14599 | rs531646671 | T | A | 0.1684410 | 0.1104720 | 0.1299999 | 0.1273241 | 0.189004 | 0.1475640 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51233182 | rs4040317 | G | A | 0.0135107 | 0.0685722 | 0.8400000 | 0.8438050 | 0.319952 | 0.2633790 | NA |
22 | 51233300 | rs9616839 | C | T | 0.0691541 | 0.0685282 | 0.3100002 | 0.3129106 | 0.332137 | 0.3146960 | NA |
22 | 51233312 | rs62240043 | A | G | 0.0575636 | 0.0721922 | 0.4299995 | 0.4252385 | 0.271944 | 0.2134580 | NA |
22 | 51233347 | rs62240044 | T | C | 0.0575636 | 0.0721922 | 0.4299995 | 0.4252385 | 0.271944 | 0.2134580 | NA |
22 | 51234799 | rs191117135 | G | A | -0.0078713 | 0.2516130 | 0.9800000 | 0.9750436 | 0.015907 | 0.0059904 | NA |
22 | 51235959 | rs200189535 | T | C | 0.0330833 | 0.0842720 | 0.6899999 | 0.6946315 | 0.193482 | 0.1996810 | NA |
22 | 51235979 | rs62240045 | G | A | -0.2114070 | 0.0933089 | 0.0230001 | 0.0234717 | 0.262466 | 0.2400160 | NA |
22 | 51236013 | rs200507571 | AT | A | 0.1292510 | 0.0715456 | 0.0710003 | 0.0708318 | 0.746643 | NA | NA |
22 | 51237063 | rs3896457 | T | C | 0.0076064 | 0.0663393 | 0.9100000 | 0.9087155 | 0.296915 | 0.2050720 | NA |
22 | 51237712 | rs370652263 | G | A | -0.0834275 | 0.1319120 | 0.5300002 | 0.5270941 | 0.055881 | 0.0690895 | NA |
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