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"gwas_harmonisation_command": "--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/vcf_09_19b/bgzip_vcf/data.batch_2784.vcf.gz --id UKB-b:9509 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_2784.txt.gz --cohort_cases 205516 --cohort_controls 44924 --ref /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/human_g1k_v37.fasta --json /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/ukb_gwas.json; 1.1.1",
"file_date": "2019-09-12T19:32:51.704585",
"bcftools_viewVersion": "1.9-74-g6af271c+htslib-1.9-64-g226b4a8",
"bcftools_viewCommand": "view -T ^/mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-9509/mac_discard.txt -Oz /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-9509/UKB-b-9509_raw.vcf.gz; Date=Thu Oct 17 12:22:31 2019",
"bcftools_viewCommand.1": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-b-9509/ukb-b-9509.vcf.gz; Date=Sun May 10 08:01:19 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/public/UKB-b-9509/UKB-b-9509_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-9509/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:42:38 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-9509/UKB-b-9509_data.vcf.gz ...
Read summary statistics for 9519492 SNPs.
Dropped 11771 SNPs with duplicated rs numbers.
Reading reference panel LD Score from ../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 ../reference/eur_w_ld_chr/[1-22] ...
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1288420 SNPs remain.
After merging with regression SNP LD, 1288420 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0205 (0.0023)
Lambda GC: 1.1423
Mean Chi^2: 1.1402
Intercept: 1.0399 (0.0071)
Ratio: 0.2848 (0.0505)
Analysis finished at Thu Oct 17 14:44:48 2019
Total time elapsed: 2.0m:9.87s
{
"af_correlation": 0.9492,
"inflation_factor": 1.0966,
"mean_EFFECT": 0,
"n": "-Inf",
"n_snps": 9851866,
"n_clumped_hits": 0,
"n_p_sig": 0,
"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": 135456,
"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": 1288420,
"ldsc_nsnp_merge_regression_ld": 1288420,
"ldsc_observed_scale_h2_beta": 0.0205,
"ldsc_observed_scale_h2_se": 0.0023,
"ldsc_intercept_beta": 1.0399,
"ldsc_intercept_se": 0.0071,
"ldsc_lambda_gc": 1.1423,
"ldsc_mean_chisq": 1.1402,
"ldsc_ratio": 0.2846
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | FALSE |
n | TRUE |
is_snpid_non_unique | FALSE |
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 | 0 | 1.0000000 | 3 | 58 | 0 | 9507781 | 0 | NA | NA | 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 | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 9519492 | 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 | 8.629018e+00 | 5.751543e+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 | 7.883506e+07 | 5.630662e+07 | 828.0000000 | 3.254473e+07 | 6.942290e+07 | 1.145654e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.440000e-05 | 4.466400e-03 | -0.0741897 | -1.540300e-03 | 6.300000e-06 | 1.563500e-03 | 7.317100e-02 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 3.326600e-03 | 2.803400e-03 | 0.0010441 | 1.266000e-03 | 2.046600e-03 | 4.522000e-03 | 3.703800e-02 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.837769e-01 | 2.929505e-01 | 0.0000004 | 2.300001e-01 | 4.799997e-01 | 7.400005e-01 | 1.000000e+00 | ▇▇▇▇▆ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.837765e-01 | 2.929239e-01 | 0.0000003 | 2.258884e-01 | 4.775306e-01 | 7.376735e-01 | 9.999998e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.094531e-01 | 2.572885e-01 | 0.0017040 | 1.563200e-02 | 8.640600e-02 | 3.277202e-01 | 9.982960e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 135456 | 0.9857707 | NA | NA | NA | NA | NA | NA | NA | 2.112126e-01 | 2.489939e-01 | 0.0000000 | 1.337860e-02 | 1.060300e-01 | 3.290730e-01 | 1.000000e+00 | ▇▂▁▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | 0.0008097 | 0.0019245 | 0.6700003 | 0.6739669 | 0.623371 | 0.7821490 | NA |
1 | 54676 | rs2462492 | C | T | 0.0013166 | 0.0019027 | 0.4899999 | 0.4889487 | 0.400972 | NA | NA |
1 | 86028 | rs114608975 | T | C | -0.0007784 | 0.0030529 | 0.8000000 | 0.7987535 | 0.103450 | 0.0277556 | NA |
1 | 91536 | rs6702460 | G | T | -0.0003987 | 0.0018746 | 0.8300000 | 0.8315843 | 0.457043 | 0.4207270 | NA |
1 | 234313 | rs8179466 | C | T | 0.0010322 | 0.0037027 | 0.7800007 | 0.7804137 | 0.074437 | NA | NA |
1 | 534192 | rs6680723 | C | T | 0.0005097 | 0.0021423 | 0.8100000 | 0.8119460 | 0.241207 | NA | NA |
1 | 546697 | rs12025928 | A | G | 0.0027765 | 0.0026728 | 0.2999998 | 0.2989146 | 0.913549 | NA | NA |
1 | 693731 | rs12238997 | A | G | 0.0000941 | 0.0017933 | 0.9599999 | 0.9581308 | 0.116696 | 0.1417730 | NA |
1 | 705882 | rs72631875 | G | A | -0.0033424 | 0.0026327 | 0.2000000 | 0.2042484 | 0.067086 | 0.0315495 | NA |
1 | 706368 | rs55727773 | A | G | -0.0013054 | 0.0013298 | 0.3300000 | 0.3262534 | 0.515101 | 0.2751600 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219704 | rs147475742 | G | A | -0.0038696 | 0.0027941 | 0.1700000 | 0.1660768 | 0.041875 | 0.0473243 | NA |
22 | 51219766 | rs182321900 | C | T | 0.0151633 | 0.0132409 | 0.2500000 | 0.2521319 | 0.001878 | NA | NA |
22 | 51220146 | rs868950473 | C | T | 0.0205412 | 0.0131160 | 0.1199999 | 0.1173211 | 0.001921 | NA | NA |
22 | 51221190 | rs369304721 | G | A | -0.0044292 | 0.0027911 | 0.1100001 | 0.1125413 | 0.049626 | NA | NA |
22 | 51221731 | rs115055839 | T | C | -0.0023642 | 0.0020858 | 0.2599998 | 0.2570029 | 0.073199 | 0.0625000 | NA |
22 | 51222100 | rs114553188 | G | T | -0.0009421 | 0.0024519 | 0.6999999 | 0.7008102 | 0.054653 | 0.0880591 | NA |
22 | 51223637 | rs375798137 | G | A | -0.0008321 | 0.0024636 | 0.7400005 | 0.7355452 | 0.054290 | 0.0788738 | NA |
22 | 51229805 | rs9616985 | T | C | -0.0024517 | 0.0020931 | 0.2399999 | 0.2414673 | 0.073071 | 0.0730831 | NA |
22 | 51232488 | rs376461333 | A | G | 0.0017123 | 0.0049305 | 0.7300002 | 0.7283739 | 0.020041 | NA | NA |
22 | 51237063 | rs3896457 | T | C | -0.0011386 | 0.0012790 | 0.3700002 | 0.3733269 | 0.297893 | 0.2050720 | NA |
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