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"gwas_harmonisation_command": "--json /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-245/ukb-a-245_data.json --ref /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/QC/genomes/b37/human_g1k_v37.fasta; 1.1.1",
"file_date": "2020-02-16T00:23:02.698543",
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"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/ukb-a-import/processed/ukb-a-245/ukb-a-245.vcf.gz -O z /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-245/ukb-a-245_data.vcf.gz; Date=Sun Feb 16 01:01:59 2020",
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"bcftools_viewCommand": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-a-245/ukb-a-245.vcf.gz; Date=Sun May 10 23:12:38 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/ukb-a-import/processed/ukb-a-245/ukb-a-245.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/ukb-a-import/processed/ukb-a-245/ldsc.txt \
--w-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/
Beginning analysis at Sun Feb 16 01:56:14 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ukb-a-import/processed/ukb-a-245/ukb-a-245.vcf.gz ...
Read summary statistics for 10877936 SNPs.
Reading reference panel LD Score from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/[1-22] ...
Read reference panel LD Scores for 1290028 SNPs.
Removing partitioned LD Scores with zero variance.
Reading regression weight LD Score from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/[1-22] ...
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1281483 SNPs remain.
After merging with regression SNP LD, 1281483 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0597 (0.0029)
Lambda GC: 1.3328
Mean Chi^2: 1.406
Intercept: 1.0221 (0.0082)
Ratio: 0.0544 (0.0203)
Analysis finished at Sun Feb 16 01:58:01 2020
Total time elapsed: 1.0m:47.73s
{
"af_correlation": 0.9533,
"inflation_factor": 1.2078,
"mean_EFFECT": 0.0001,
"n": 327528,
"n_snps": 10877936,
"n_clumped_hits": 20,
"n_p_sig": 988,
"n_mono": 0,
"n_ns": 0,
"n_mac": 0,
"is_snpid_unique": true,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 0,
"n_miss_AF_reference": 356865,
"n_est": 326091.3984,
"ratio_se_n": 0.9978,
"mean_diff": 0,
"ratio_diff": 8.263,
"sd_y_est1": 0.8277,
"sd_y_est2": 0.8259,
"r2_sum1": 0.0015,
"r2_sum2": 0.0022,
"r2_sum3": 0.0023,
"r2_sum4": 0.0022,
"ldsc_nsnp_merge_refpanel_ld": 1281483,
"ldsc_nsnp_merge_regression_ld": 1281483,
"ldsc_observed_scale_h2_beta": 0.0597,
"ldsc_observed_scale_h2_se": 0.0029,
"ldsc_intercept_beta": 1.0221,
"ldsc_intercept_se": 0.0082,
"ldsc_lambda_gc": 1.3328,
"ldsc_mean_chisq": 1.406,
"ldsc_ratio": 0.0544
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | TRUE |
n | FALSE |
is_snpid_non_unique | FALSE |
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 | 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 | numeric.mean | numeric.sd | numeric.p0 | numeric.p25 | numeric.p50 | numeric.p75 | numeric.p100 | numeric.hist |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
character | ID | 0 | 1.0000000 | 3 | 58 | 0 | 10877936 | 0 | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA |
numeric | CHROM | 0 | 1.0000000 | NA | NA | NA | NA | NA | 8.598638e+00 | 5.745666e+00 | 1.00000e+00 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▃▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.911383e+07 | 5.624931e+07 | 8.28000e+02 | 3.287294e+07 | 6.988889e+07 | 1.148258e+08 | 2.492251e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | 6.890000e-05 | 1.247070e-02 | -1.40088e-01 | -3.640400e-03 | 3.210000e-05 | 3.706500e-03 | 1.611170e-01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 8.808600e-03 | 8.342900e-03 | 2.02060e-03 | 2.495900e-03 | 4.793800e-03 | 1.280880e-02 | 4.591460e-02 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.690249e-01 | 2.974686e-01 | 0.00000e+00 | 2.035720e-01 | 4.585250e-01 | 7.269123e-01 | 1.000000e+00 | ▇▆▆▆▆ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.690244e-01 | 2.974689e-01 | 0.00000e+00 | 2.035713e-01 | 4.585242e-01 | 7.269121e-01 | 9.999999e-01 | ▇▆▆▆▆ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | 1.820865e-01 | 2.503832e-01 | 1.00090e-03 | 6.878700e-03 | 5.191440e-02 | 2.739880e-01 | 9.989990e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 356865 | 0.9671937 | NA | NA | NA | NA | NA | 1.877709e-01 | 2.439191e-01 | 0.00000e+00 | 5.191700e-03 | 7.468050e-02 | 2.873400e-01 | 1.000000e+00 | ▇▂▁▁▁ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | 3.275280e+05 | 0.000000e+00 | 3.27528e+05 | 3.275280e+05 | 3.275280e+05 | 3.275280e+05 | 3.275280e+05 | ▁▁▇▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 693731 | rs12238997 | A | G | 0.0032208 | 0.0033731 | 0.3396620 | 0.3396600 | 0.1169260 | 0.1417730 | 327528 |
1 | 717587 | rs144155419 | G | A | 0.0028504 | 0.0090640 | 0.7531578 | 0.7531582 | 0.0143862 | 0.0045926 | 327528 |
1 | 730087 | rs148120343 | T | C | 0.0050300 | 0.0047017 | 0.2847030 | 0.2847018 | 0.0554733 | 0.0127796 | 327528 |
1 | 731718 | rs142557973 | T | C | 0.0022791 | 0.0032002 | 0.4763553 | 0.4763539 | 0.1216580 | 0.1543530 | 327528 |
1 | 734349 | rs141242758 | T | C | 0.0024735 | 0.0032020 | 0.4398281 | 0.4398267 | 0.1215130 | 0.1525560 | 327528 |
1 | 740284 | rs61770167 | C | T | -0.0098200 | 0.0145494 | 0.4997111 | 0.4997109 | 0.0058556 | 0.0023962 | 327528 |
1 | 742813 | rs112573343 | C | T | -0.0011705 | 0.0274993 | 0.9660491 | 0.9660494 | 0.0015525 | 0.1030350 | 327528 |
1 | 753405 | rs3115860 | C | A | -0.0025846 | 0.0030423 | 0.3955824 | 0.3955816 | 0.8706760 | 0.7517970 | 327528 |
1 | 753541 | rs2073813 | G | A | 0.0024915 | 0.0030499 | 0.4139816 | 0.4139811 | 0.1288330 | 0.3019170 | 327528 |
1 | 754182 | rs3131969 | A | G | -0.0024466 | 0.0030391 | 0.4207974 | 0.4207968 | 0.8703180 | 0.6785140 | 327528 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219387 | rs9616832 | T | C | 0.0020699 | 0.0039192 | 0.5974011 | 0.5974013 | 0.0729806 | 0.0654952 | 327528 |
22 | 51219704 | rs147475742 | G | A | 0.0012448 | 0.0052551 | 0.8127590 | 0.8127600 | 0.0418225 | 0.0473243 | 327528 |
22 | 51219766 | rs182321900 | C | T | 0.0149712 | 0.0270291 | 0.5796542 | 0.5796528 | 0.0014546 | NA | 327528 |
22 | 51220088 | rs566371895 | G | A | -0.0188745 | 0.0177376 | 0.2872890 | 0.2872854 | 0.0039843 | 0.0003994 | 327528 |
22 | 51220146 | rs868950473 | C | T | 0.0162663 | 0.0266328 | 0.5413561 | 0.5413572 | 0.0015139 | NA | 327528 |
22 | 51221731 | rs115055839 | T | C | 0.0020273 | 0.0039218 | 0.6051987 | 0.6051981 | 0.0728101 | 0.0625000 | 327528 |
22 | 51223637 | rs375798137 | G | A | -0.0035622 | 0.0046207 | 0.4407588 | 0.4407589 | 0.0540289 | 0.0788738 | 327528 |
22 | 51226692 | rs150189434 | G | A | 0.0247914 | 0.0276572 | 0.3700514 | 0.3700491 | 0.0013983 | 0.0155751 | 327528 |
22 | 51229805 | rs9616985 | T | C | 0.0017925 | 0.0039364 | 0.6488376 | 0.6488368 | 0.0727671 | 0.0730831 | 327528 |
22 | 51237063 | rs3896457 | T | C | 0.0028836 | 0.0023952 | 0.2286378 | 0.2286362 | 0.2968410 | 0.2050720 | 327528 |
1 693731 rs12238997 A G . PASS AF=0.116926 ES:SE:LP:AF:SS:ID 0.00322079:0.00337313:0.468953:0.116926:327528:rs12238997
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1 740284 rs61770167 C T . PASS AF=0.00585559 ES:SE:LP:AF:SS:ID -0.00982004:0.0145494:0.301281:0.00585559:327528:rs61770167
1 742813 rs112573343 C T . PASS AF=0.0015525 ES:SE:LP:AF:SS:ID -0.00117047:0.0274993:0.0150008:0.0015525:327528:rs112573343
1 753405 rs3115860 C A . PASS AF=0.870676 ES:SE:LP:AF:SS:ID -0.00258456:0.00304231:0.402763:0.870676:327528:rs3115860
1 753541 rs2073813 G A . PASS AF=0.128833 ES:SE:LP:AF:SS:ID 0.00249152:0.00304994:0.383019:0.128833:327528:rs2073813
1 754182 rs3131969 A G . PASS AF=0.870318 ES:SE:LP:AF:SS:ID -0.00244658:0.00303908:0.375927:0.870318:327528:rs3131969
1 754192 rs3131968 A G . PASS AF=0.870409 ES:SE:LP:AF:SS:ID -0.00225716:0.00304054:0.339256:0.870409:327528:rs3131968
1 754334 rs3131967 T C . PASS AF=0.870037 ES:SE:LP:AF:SS:ID -0.00246498:0.00303896:0.379558:0.870037:327528:rs3131967
1 754433 rs150578204 G A . PASS AF=0.00465304 ES:SE:LP:AF:SS:ID -0.00531602:0.0155422:0.135297:0.00465304:327528:rs150578204
1 754458 rs142682604 G T . PASS AF=0.00464711 ES:SE:LP:AF:SS:ID -0.00545043:0.0155848:0.138739:0.00464711:327528:rs142682604
1 755435 rs184270342 T G . PASS AF=0.00590897 ES:SE:LP:AF:SS:ID -0.0160995:0.0150843:0.543882:0.00590897:327528:rs184270342
1 755890 rs3115858 A T . PASS AF=0.870329 ES:SE:LP:AF:SS:ID -0.00265187:0.00303366:0.417895:0.870329:327528:rs3115858
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1 770377 rs112563271 A T . PASS AF=0.00692321 ES:SE:LP:AF:SS:ID -0.00065906:0.0123643:0.0188658:0.00692321:327528:rs112563271
1 771823 rs2977605 T C . PASS AF=0.869934 ES:SE:LP:AF:SS:ID -0.0025224:0.00303178:0.392098:0.869934:327528:rs2977605
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1 772755 rs2905039 A C . PASS AF=0.870112 ES:SE:LP:AF:SS:ID -0.00248586:0.00303194:0.38481:0.870112:327528:rs2905039
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1 777122 rs2980319 A T . PASS AF=0.871122 ES:SE:LP:AF:SS:ID -0.00232073:0.00303714:0.351837:0.871122:327528:rs2980319
1 777232 rs112618790 C T . PASS AF=0.0961319 ES:SE:LP:AF:SS:ID 0.000276732:0.00350542:0.0282247:0.0961319:327528:rs112618790
1 778745 rs1055606 A G . PASS AF=0.127871 ES:SE:LP:AF:SS:ID 0.00225345:0.00304716:0.337631:0.127871:327528:rs1055606
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1 781845 rs61768199 A G . PASS AF=0.1044 ES:SE:LP:AF:SS:ID 0.00235269:0.00340953:0.30965:0.1044:327528:rs61768199
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1 782981 rs6594026 C T . PASS AF=0.128338 ES:SE:LP:AF:SS:ID 0.00182739:0.00304469:0.260918:0.128338:327528:rs6594026
1 783193 rs145767270 G C . PASS AF=0.0143639 ES:SE:LP:AF:SS:ID -0.00489368:0.00927645:0.22343:0.0143639:327528:rs145767270
1 783194 rs138555831 G T . PASS AF=0.0143713 ES:SE:LP:AF:SS:ID -0.00480544:0.00927529:0.218679:0.0143713:327528:rs138555831
1 783711 rs184266993 G A . PASS AF=0.00541372 ES:SE:LP:AF:SS:ID -0.0090284:0.0147864:0.266423:0.00541372:327528:rs184266993
1 785050 rs2905062 G A . PASS AF=0.87014 ES:SE:LP:AF:SS:ID -0.00211935:0.0030326:0.314578:0.87014:327528:rs2905062
1 785989 rs2980300 T C . PASS AF=0.87009 ES:SE:LP:AF:SS:ID -0.00213575:0.00303456:0.317356:0.87009:327528:rs2980300