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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/0f4c6086-f5d8-4310-9a9d-8ba6720dc8ae/call-vcf/inputs/-261022253/upload.txt.gz --id ieu-b-5071 --json /data/cromwell-executions/qc/0f4c6086-f5d8-4310-9a9d-8ba6720dc8ae/call-vcf/inputs/-261022253/ieu-b-5071_data.json --ref /data/cromwell-executions/qc/0f4c6086-f5d8-4310-9a9d-8ba6720dc8ae/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/0f4c6086-f5d8-4310-9a9d-8ba6720dc8ae/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-5071/ieu-b-5071.vcf.gz --alias alias.txt; 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/0f4c6086-f5d8-4310-9a9d-8ba6720dc8ae/call-ldsc/inputs/-261022253/ieu-b-5071.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-5071/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Sun May 15 17:59:36 2022
Reading summary statistics from /data/cromwell-executions/qc/0f4c6086-f5d8-4310-9a9d-8ba6720dc8ae/call-ldsc/inputs/-261022253/ieu-b-5071.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 Sun May 15 18:01:02 2022
Total time elapsed: 1.0m:25.98s
{
"af_correlation": 0.9272,
"inflation_factor": 1.0475,
"mean_EFFECT": "NaN",
"n": "-Inf",
"n_snps": 13525533,
"n_clumped_hits": 5,
"n_p_sig": 910,
"n_mono": 47833,
"n_ns": 930519,
"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": 2715836,
"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 | TRUE |
mean_EFFECT_05 | NA |
mean_EFFECT_01 | NA |
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 | 568685 | 0.9579547 | 3 | 12 | 0 | 12944390 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 101 | 0 | 16685 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 342 | 0 | 73633 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 13525533 | 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 | 8.751170e+00 | 5.959679e+00 | 1.0000e+00 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 23 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 7.981845e+07 | 5.497535e+07 | 3.0200e+02 | 3.498962e+07 | 7.150886e+07 | 1.144903e+08 | 249220724 | ▇▇▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | NaN | NaN | -Inf | -1.040540e-02 | 5.530000e-05 | 1.063960e-02 | Inf | ▁▁▁▇▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | Inf | NaN | 3.4984e-03 | 6.130400e-03 | 1.746360e-02 | 5.988120e-02 | Inf | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.942361e-01 | 2.922202e-01 | 0.0000e+00 | 2.399999e-01 | 4.899999e-01 | 7.499995e-01 | 1 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 14331 | 0.9989404 | NA | NA | NA | NA | NA | NA | NA | 4.936993e-01 | 2.918833e-01 | 0.0000e+00 | 2.389015e-01 | 4.912973e-01 | 7.465426e-01 | 1 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.033787e-01 | 2.966140e-01 | 0.0000e+00 | 2.064000e-03 | 3.008700e-02 | 3.154760e-01 | 1 | ▇▁▁▁▁ |
numeric | AF_reference | 2715836 | 0.7992067 | NA | NA | NA | NA | NA | NA | NA | 1.839050e-01 | 2.407114e-01 | 0.0000e+00 | 9.984000e-04 | 6.948880e-02 | 2.945290e-01 | 1 | ▇▂▁▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 751343 | rs28544273 | T | A | -0.0039229 | 0.0069701 | 0.5700002 | 0.5735576 | 0.147575 | 0.242612 | NA |
1 | 751756 | rs143225517 | T | C | -0.0038510 | 0.0069538 | 0.5800000 | 0.5797196 | 0.147109 | 0.242212 | NA |
1 | 752566 | rs3094315 | G | A | 0.0041934 | 0.0064371 | 0.5099998 | 0.5147576 | 0.842815 | 0.718251 | NA |
1 | 752894 | rs3131971 | T | C | 0.0041260 | 0.0067790 | 0.5400003 | 0.5427653 | 0.849755 | 0.753195 | NA |
1 | 753405 | rs3115860 | C | A | 0.0038270 | 0.0069041 | 0.5800000 | 0.5793690 | 0.851609 | 0.751797 | NA |
1 | 753425 | rs3131970 | T | C | 0.0038549 | 0.0068751 | 0.5700002 | 0.5749975 | 0.850948 | 0.749002 | NA |
1 | 756285 | rs1557551112 | A | ATCCACCCTGTCTACACTACCTGCTTGTCCAGCAGG | 0.0058722 | 0.0073375 | 0.4199997 | 0.4235369 | 0.859010 | NA | NA |
1 | 759293 | rs10157329 | T | A | -0.0006318 | 0.0081929 | 0.9400001 | 0.9385334 | 0.122653 | 0.154153 | NA |
1 | 759700 | rs989694037 | T | C | 0.0039961 | 0.0067576 | 0.5500004 | 0.5542929 | 0.845951 | NA | NA |
1 | 759837 | rs114111569 | T | A | 0.0037049 | 0.0069766 | 0.5999997 | 0.5953885 | 0.850978 | 0.752596 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
23 | 154819368 | rs782310 | T | C | 0.0046693 | 0.0047907 | 0.3300000 | 0.3297313 | 0.774235 | 0.6439740 | NA |
23 | 154821956 | rs5940536 | G | A | -0.0334376 | 0.0450422 | 0.4600002 | 0.4578683 | 0.001536 | 0.0389404 | NA |
23 | 154822874 | rs1084450 | A | T | 0.0046884 | 0.0048214 | 0.3300000 | 0.3308424 | 0.774002 | 0.6439740 | NA |
23 | 154825665 | rs782308 | T | A | 0.0047232 | 0.0048550 | 0.3300000 | 0.3306174 | 0.773338 | 0.6439740 | NA |
23 | 154826161 | rs782307 | G | C | 0.0051690 | 0.0048344 | 0.2800000 | 0.2849728 | 0.763587 | 0.5343050 | NA |
23 | 154826774 | rs782306 | G | A | 0.0047336 | 0.0048666 | 0.3300000 | 0.3307139 | 0.772455 | 0.6384110 | NA |
23 | 154827160 | rs809138 | T | C | 0.0046911 | 0.0048738 | 0.3400001 | 0.3357914 | 0.772675 | 0.6381460 | NA |
23 | 154827280 | rs5983745 | T | C | 0.0046883 | 0.0048816 | 0.3400001 | 0.3368588 | 0.773356 | 0.6442380 | NA |
23 | 154830377 | rs5983658 | C | T | 0.0047449 | 0.0049175 | 0.3300000 | 0.3345875 | 0.771466 | 0.6384110 | NA |
23 | 154830744 | rs10782079 | A | G | 0.0047483 | 0.0049302 | 0.3400001 | 0.3354927 | 0.771938 | 0.6439740 | NA |
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