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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/a9dc6490-7195-4a9d-b1f7-ae6de0424d1e/call-vcf/inputs/-261044352/upload.txt.gz --id ieu-b-4875 --json /data/cromwell-executions/qc/a9dc6490-7195-4a9d-b1f7-ae6de0424d1e/call-vcf/inputs/-261044352/ieu-b-4875_data.json --ref /data/cromwell-executions/qc/a9dc6490-7195-4a9d-b1f7-ae6de0424d1e/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/a9dc6490-7195-4a9d-b1f7-ae6de0424d1e/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-4875/ieu-b-4875.vcf.gz --alias alias.txt --cohort_cases 606 --cohort_controls 372016; 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/a9dc6490-7195-4a9d-b1f7-ae6de0424d1e/call-ldsc/inputs/-261044352/ieu-b-4875.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4875/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Fri Jan 28 02:27:39 2022
Reading summary statistics from /data/cromwell-executions/qc/a9dc6490-7195-4a9d-b1f7-ae6de0424d1e/call-ldsc/inputs/-261044352/ieu-b-4875.vcf.gz ...
Read summary statistics for 8628176 SNPs.
Dropped 152978 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, 1185809 SNPs remain.
After merging with regression SNP LD, 1185809 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0018 (0.0012)
Lambda GC: 1.0142
Mean Chi^2: 1.0181
Intercept: 1.0051 (0.0058)
Ratio: 0.2799 (0.3218)
Analysis finished at Fri Jan 28 02:29:28 2022
Total time elapsed: 1.0m:49.08s
{
"af_correlation": 0.9327,
"inflation_factor": 1,
"mean_EFFECT": 7.5525e-08,
"n": "-Inf",
"n_snps": 8629116,
"n_clumped_hits": 2,
"n_p_sig": 106,
"n_mono": 0,
"n_ns": 1064956,
"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": 1065881,
"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": 1185809,
"ldsc_nsnp_merge_regression_ld": 1185809,
"ldsc_observed_scale_h2_beta": 0.0018,
"ldsc_observed_scale_h2_se": 0.0012,
"ldsc_intercept_beta": 1.0051,
"ldsc_intercept_se": 0.0058,
"ldsc_lambda_gc": 1.0142,
"ldsc_mean_chisq": 1.0181,
"ldsc_ratio": 0.2818
}
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
(\(2 \times N \times MAF\)) 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 | 612 | 0.9999291 | 3 | 58 | 0 | 8601110 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 88 | 0 | 14117 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 662 | 0 | 58260 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 8629116 | 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 | 8.850675e+00 | 5.948850e+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 | 7.840903e+07 | 5.641432e+07 | 302.0000000 | 3.200491e+07 | 6.882032e+07 | 1.143424e+08 | 2.492405e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.000000e-07 | 1.670000e-04 | -0.0014486 | -9.290000e-05 | -9.000000e-07 | 9.150000e-05 | 1.618200e-03 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.527000e-04 | 6.560000e-05 | 0.0000767 | 1.008000e-04 | 1.254000e-04 | 1.877000e-04 | 7.892000e-04 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.976503e-01 | 2.889851e-01 | 0.0000000 | 2.500000e-01 | 5.000000e-01 | 7.499995e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.976511e-01 | 2.889609e-01 | 0.0000000 | 2.469694e-01 | 4.967509e-01 | 7.480756e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 3.355528e-01 | 2.872367e-01 | 0.0206280 | 8.209370e-02 | 2.432710e-01 | 5.446900e-01 | 9.793720e-01 | ▇▃▂▂▂ |
numeric | AF_reference | 1065881 | 0.8764785 | NA | NA | NA | NA | NA | NA | NA | 2.913407e-01 | 2.519120e-01 | 0.0000000 | 8.266770e-02 | 2.146570e-01 | 4.522760e-01 | 1.000000e+00 | ▇▃▂▂▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 10177 | rs1264289758 | AC | A | -0.0001677 | 0.0001394 | 0.2300001 | 0.2288946 | 0.601321 | NA | NA |
1 | 10352 | rs1557426776 | TA | T | -0.0002714 | 0.0001435 | 0.0589997 | 0.0586857 | 0.606977 | NA | NA |
1 | 11008 | rs575272151 | C | G | -0.0001365 | 0.0002387 | 0.5700002 | 0.5673794 | 0.086188 | 0.0880591 | NA |
1 | 11012 | rs544419019 | C | G | -0.0001365 | 0.0002387 | 0.5700002 | 0.5673794 | 0.086188 | 0.0880591 | NA |
1 | 13110 | rs540538026 | G | A | -0.0002951 | 0.0003171 | 0.3500000 | 0.3519011 | 0.058732 | 0.0267572 | NA |
1 | 13116 | rs62635286 | T | G | -0.0002733 | 0.0001878 | 0.1499999 | 0.1455959 | 0.189403 | 0.0970447 | NA |
1 | 13118 | rs200579949 | A | G | -0.0002733 | 0.0001878 | 0.1499999 | 0.1455959 | 0.189403 | 0.0970447 | NA |
1 | 13273 | rs531730856 | G | C | 0.0002411 | 0.0002201 | 0.2700001 | 0.2733569 | 0.133943 | 0.0950479 | NA |
1 | 14464 | rs546169444 | A | T | -0.0001907 | 0.0001999 | 0.3400001 | 0.3401707 | 0.157043 | 0.0958466 | NA |
1 | 14599 | rs531646671 | T | A | -0.0001278 | 0.0001822 | 0.4799997 | 0.4830278 | 0.191564 | 0.1475640 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
23 | 154901936 | rs697727 | A | G | 0.0002262 | 8.92e-05 | 0.0109999 | 0.0112673 | 0.751559 | 0.643179 | NA |
23 | 154901964 | rs697726 | G | A | 0.0000733 | 9.42e-05 | 0.4400003 | 0.4363035 | 0.347491 | 0.117616 | NA |
23 | 154902105 | rs696316 | G | T | 0.0002264 | 8.92e-05 | 0.0109999 | 0.0111867 | 0.751511 | 0.636026 | NA |
23 | 154902889 | rs697725 | A | T | 0.0002280 | 8.92e-05 | 0.0109999 | 0.0105822 | 0.751183 | 0.584106 | NA |
23 | 154903118 | rs479770 | G | A | 0.0002259 | 8.93e-05 | 0.0109999 | 0.0113760 | 0.751601 | 0.643444 | NA |
23 | 154903224 | rs480725 | A | T | 0.0002259 | 8.93e-05 | 0.0109999 | 0.0113671 | 0.751604 | 0.643444 | NA |
23 | 154903937 | rs674707 | G | A | 0.0002258 | 8.93e-05 | 0.0109999 | 0.0113969 | 0.751614 | 0.643444 | NA |
23 | 154909055 | rs473529 | C | G | -0.0001152 | 8.40e-05 | 0.1700000 | 0.1704450 | 0.305079 | 0.463046 | NA |
23 | 154918266 | rs642043 | C | T | -0.0001137 | 8.43e-05 | 0.1800002 | 0.1775061 | 0.302944 | 0.478675 | NA |
23 | 154927581 | rs644138 | G | A | -0.0001134 | 8.43e-05 | 0.1800002 | 0.1787419 | 0.302816 | 0.463576 | NA |
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