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"FORMAT.2": "<ID=EZ,Number=A,Type=Float,Description=\"Z-score provided if it was used to derive the EFFECT and SE fields\">",
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"gwas_harmonisation_command": "--json /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/processed/EBI-a-GCST005353/EBI-a-GCST005353_data.json --ref /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/QC/genomes/hg38/hg38.fa; 1.1.1",
"reference": "file:/mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/QC/genomes/b37/human_g1k_v37.fasta",
"bcftools_annotateVersion": "1.9-74-g6af271c+htslib-1.9-64-g226b4a8",
"bcftools_annotateCommand": "annotate -a /mnt/storage/home/gh13047/mr-eve/vcf-reference-datasets/dbsnp/dbsnp.v153.b37.vcf.gz -c ID -o /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/processed/EBI-a-GCST005353/EBI-a-GCST005353.vcf.gz -O z /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/processed/EBI-a-GCST005353/EBI-a-GCST005353_data.vcf.gz; Date=Sat Oct 26 21:58:27 2019",
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"bcftools_viewCommand": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ebi-a-GCST005353/ebi-a-GCST005353.vcf.gz; Date=Sun May 10 10:48:45 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/dev/ebi_gwas_import/processed/EBI-a-GCST005353/EBI-a-GCST005353.vcf.gz \
--ref-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/processed/EBI-a-GCST005353/ldsc.txt \
--snplist /data/ref/snplist.gz \
--w-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/
Beginning analysis at Sat Oct 26 22:21:48 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/processed/EBI-a-GCST005353/EBI-a-GCST005353.vcf.gz ...
and extracting SNPs specified in /data/ref/snplist.gz ...
Traceback (most recent call last):
File "./ldsc/ldsc.py", line 647, in <module>
sumstats.estimate_h2(args, log)
File "/mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/igd-hpc-pipeline/resources/gwas_processing/ldsc/ldscore/sumstats.py", line 330, in estimate_h2
args, log, args.h2)
File "/mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/igd-hpc-pipeline/resources/gwas_processing/ldsc/ldscore/sumstats.py", line 246, in _read_ld_sumstats
sumstats = _read_sumstats(args, log, fh, alleles=alleles, dropna=dropna)
File "/mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/igd-hpc-pipeline/resources/gwas_processing/ldsc/ldscore/sumstats.py", line 165, in _read_sumstats
sumstats = ps.sumstats(fh, alleles=alleles, dropna=dropna, slh=args.snplist)
File "/mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/igd-hpc-pipeline/resources/gwas_processing/ldsc/ldscore/parse.py", line 85, in sumstats
x = read_vcf(fh, alleles, slh)
File "/mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ebi_gwas_import/igd-hpc-pipeline/resources/gwas_processing/ldsc/ldscore/parse.py", line 140, in read_vcf
o = [[rec.id, rec.samples[sample]['ES'][0]/rec.samples[sample]['SE'][0]] for rec in vcf_in.fetch()]
ZeroDivisionError: float division by zero
Analysis finished at Sat Oct 26 22:21:49 2019
Total time elapsed: 0.45s
{
"af_correlation": 0.9,
"inflation_factor": 1.1118,
"mean_EFFECT": -0.0004,
"n": "-Inf",
"n_snps": 6463530,
"n_clumped_hits": 0,
"n_p_sig": 0,
"n_mono": 0,
"n_ns": 459086,
"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": 332142,
"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": "NA",
"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 | TRUE |
n_p_sig | FALSE |
miss_EFFECT | FALSE |
miss_SE | FALSE |
miss_PVAL | FALSE |
ldsc_ratio | TRUE |
ldsc_intercept_beta | TRUE |
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 | 59 | 0 | 6441878 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 25 | 0 | 14405 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 25 | 0 | 12305 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 6442494 | 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 | 9.062274e+00 | 6.144661e+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 | 7.853104e+07 | 5.634929e+07 | 302.0000000 | 3.199851e+07 | 6.934810e+07 | 1.146711e+08 | 2.492298e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -3.593000e-04 | 1.617620e-01 | -15.7897000 | -9.727000e-02 | -4.200000e-04 | 9.629000e-02 | 1.444210e+01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.385984e-01 | 4.314750e-02 | 0.0000000 | 1.059100e-01 | 1.238400e-01 | 1.619100e-01 | 1.562660e+00 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.835761e-01 | 2.921123e-01 | 0.0000018 | 2.262440e-01 | 4.769721e-01 | 7.360291e-01 | 9.999942e-01 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.705015e-01 | 2.946229e-01 | 0.0000000 | 2.080180e-01 | 4.578012e-01 | 7.248036e-01 | 9.999734e-01 | ▇▇▆▆▆ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 3.341909e-01 | 2.461896e-01 | 0.0500100 | 1.236200e-01 | 2.615900e-01 | 5.010600e-01 | 9.499900e-01 | ▇▃▂▂▂ |
numeric | AF_reference | 332142 | 0.9484451 | NA | NA | NA | NA | NA | NA | NA | 3.313113e-01 | 2.419700e-01 | 0.0000000 | 1.317890e-01 | 2.703670e-01 | 4.948080e-01 | 1.000000e+00 | ▇▆▃▂▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 54421 | rs146477069 | A | G | -0.22778 | 0.36695 | 0.6880056 | 0.5347717 | 0.08284 | NA | NA |
1 | 55249 | rs200769871 | C | CTATGG | -0.07369 | 0.36665 | 0.8870192 | 0.8407128 | 0.06373 | NA | NA |
1 | 55299 | rs10399749 | C | T | -0.11758 | 0.20942 | 0.7147119 | 0.5744871 | 0.20671 | NA | NA |
1 | 57321 | rs1244179854 | G | A | -4.92046 | 0.00000 | 0.9298498 | 0.0000000 | 0.15383 | NA | NA |
1 | 77874 | rs62641297 | G | A | 0.20467 | 0.30362 | 0.6648903 | 0.5002482 | 0.07767 | 0.0547125 | NA |
1 | 84005 | rs202079949 | AG | A | -0.08858 | 0.26267 | 0.8213034 | 0.7359441 | 0.06338 | NA | NA |
1 | 88169 | rs940550 | C | T | -0.06506 | 0.24409 | 0.8654720 | 0.7898226 | 0.17881 | 0.2993210 | NA |
1 | 88338 | rs55700207 | G | A | 0.07204 | 0.30069 | 0.8754600 | 0.8106541 | 0.10143 | 0.0940495 | NA |
1 | 89946 | rs138808727 | A | T | -0.31236 | 0.16219 | 0.2134460 | 0.0541182 | 0.23900 | 0.1226040 | NA |
1 | 92858 | rs147061536 | G | T | -0.35013 | 0.16379 | 0.1737101 | 0.0325430 | 0.22950 | 0.1349840 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
23 | 154918383 | rs641588 | G | T | 0.04554 | 0.10724 | 0.6752911 | 0.6710882 | 0.19562 | 0.356556 | NA |
23 | 154925045 | rs509981 | C | T | 0.04549 | 0.10738 | 0.6762262 | 0.6718315 | 0.19527 | 0.363444 | NA |
23 | 154925893 | rs201173655 | C | CAT | -0.06337 | 0.22977 | 0.8501137 | 0.7827036 | 0.06163 | NA | NA |
23 | 154925895 | rs538470 | C | T | 0.00787 | 0.11569 | 0.9486218 | 0.9457644 | 0.19549 | 0.363444 | NA |
23 | 154927185 | rs185685661 | T | C | 0.22448 | 0.21767 | 0.4356252 | 0.3024068 | 0.10682 | 0.179603 | NA |
23 | 154927197 | rs200614200 | TAC | T | 0.04497 | 0.10780 | 0.6814343 | 0.6765603 | 0.19424 | NA | NA |
23 | 154927199 | rs645904 | C | T | 0.04549 | 0.10737 | 0.6762356 | 0.6718027 | 0.19527 | 0.367417 | NA |
23 | 154927581 | rs644138 | G | A | 0.02709 | 0.11113 | 0.8220882 | 0.8074101 | 0.22898 | 0.463576 | NA |
23 | 154929412 | rs557132 | C | T | 0.04589 | 0.10748 | 0.6750361 | 0.6694062 | 0.19631 | 0.356821 | NA |
23 | 154930230 | rs781880 | A | G | 0.04625 | 0.10913 | 0.6781988 | 0.6717070 | 0.19423 | 0.361854 | NA |
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1 754182 rs3131969 A G . PASS AF=0.8556 ES:SE:LP:AF:ID 0.19079:0.14939:0.67387:0.8556:rs3131969
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1 754334 rs3131967 T C . PASS AF=0.82033 ES:SE:LP:AF:ID 0.1639:0.14879:0.468729:0.82033:rs3131967
1 754503 rs3115859 G A . PASS AF=0.8512 ES:SE:LP:AF:ID 0.17299:0.14523:0.622635:0.8512:rs3115859
1 754964 rs3131966 C T . PASS AF=0.82439 ES:SE:LP:AF:ID 0.14221:0.14497:0.418885:0.82439:rs3131966
1 755775 rs3131965 A G . PASS AF=0.79203 ES:SE:LP:AF:ID 0.19702:0.15209:0.591082:0.79203:rs3131965
1 755890 rs3115858 A T . PASS AF=0.85372 ES:SE:LP:AF:ID 0.18542:0.14874:0.639834:0.85372:rs3115858
1 756604 rs3131962 A G . PASS AF=0.83353 ES:SE:LP:AF:ID 0.10759:0.14518:0.29539:0.83353:rs3131962