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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_41202_Z538.vcf.gz --id UKB-b:9696 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_41202_Z538.txt.gz --cohort_cases 1155 --cohort_controls 461855 --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": "2019-09-13T07:13:52.203216",
"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-9696/mac_discard.txt -Oz /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-9696/UKB-b-9696_raw.vcf.gz; Date=Thu Oct 17 12:22:55 2019",
"bcftools_viewCommand.1": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-b-9696/ukb-b-9696.vcf.gz; Date=Sat May 9 20:22:12 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-9696/UKB-b-9696_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-9696/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:42:51 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-9696/UKB-b-9696_data.vcf.gz ...
Read summary statistics for 1781739 SNPs.
Dropped 169 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, 458882 SNPs remain.
After merging with regression SNP LD, 458882 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0019 (0.0016)
Lambda GC: 1.0782
Mean Chi^2: 1.0865
Intercept: 1.0654 (0.0124)
Ratio: 0.7558 (0.1433)
Analysis finished at Thu Oct 17 14:43:18 2019
Total time elapsed: 27.11s
{
"af_correlation": 0.6544,
"inflation_factor": 1.0966,
"mean_EFFECT": -8.03e-07,
"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": 14090,
"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": 458882,
"ldsc_nsnp_merge_regression_ld": 458882,
"ldsc_observed_scale_h2_beta": 0.0019,
"ldsc_observed_scale_h2_se": 0.0016,
"ldsc_intercept_beta": 1.0654,
"ldsc_intercept_se": 0.0124,
"ldsc_lambda_gc": 1.0782,
"ldsc_mean_chisq": 1.0865,
"ldsc_ratio": 0.7561
}
name | value |
---|---|
af_correlation | TRUE |
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 | TRUE |
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 | 1.000000 | 4 | 58 | 0 | 1781572 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 1781739 | 0.000000 | NA | NA | NA | NA | NA | NaN | : | NA | NA | NA | NA | NA | NA | NA | NA |
numeric | CHROM | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 8.655580e+00 | 5.766071e+00 | 1.00000e+00 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 7.869658e+07 | 5.664718e+07 | 1.23330e+04 | 3.178970e+07 | 6.928345e+07 | 1.148325e+08 | 2.491722e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | -8.000000e-07 | 1.117000e-04 | -6.03900e-04 | -7.540000e-05 | -9.000000e-07 | 7.410000e-05 | 6.485000e-04 | ▁▂▇▁▁ |
numeric | SE | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 1.071000e-04 | 3.400000e-06 | 1.00000e-04 | 1.045000e-04 | 1.062000e-04 | 1.091000e-04 | 2.030000e-04 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 4.871137e-01 | 2.923389e-01 | 1.10000e-05 | 2.300001e-01 | 4.799997e-01 | 7.400005e-01 | 1.000000e+00 | ▇▇▇▇▆ |
numeric | PVAL_ztest | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 4.871178e-01 | 2.923101e-01 | 1.14000e-05 | 2.296634e-01 | 4.848795e-01 | 7.402635e-01 | 9.999996e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 4.754184e-01 | 1.129396e-01 | 3.03031e-01 | 3.760965e-01 | 4.629150e-01 | 5.684965e-01 | 6.969680e-01 | ▇▇▆▅▅ |
numeric | AF_reference | 14090 | 0.992092 | NA | NA | NA | NA | NA | NA | NA | 4.544419e-01 | 1.536519e-01 | 1.99700e-04 | 3.376600e-01 | 4.466850e-01 | 5.650960e-01 | 1.000000e+00 | ▁▇▇▃▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | 0.0000833 | 0.0001839 | 0.6499995 | 0.6505504 | 0.623765 | 0.782149 | NA |
1 | 54676 | rs2462492 | C | T | -0.0001905 | 0.0001822 | 0.2999998 | 0.2959100 | 0.400401 | NA | NA |
1 | 91536 | rs6702460 | G | T | -0.0000388 | 0.0001794 | 0.8300000 | 0.8286370 | 0.456846 | 0.420727 | NA |
1 | 706368 | rs55727773 | A | G | -0.0000891 | 0.0001272 | 0.4799997 | 0.4836873 | 0.515645 | 0.275160 | NA |
1 | 814495 | rs74461805 | C | A | 0.0000943 | 0.0001745 | 0.5900000 | 0.5886849 | 0.340396 | NA | NA |
1 | 840753 | rs4970382 | T | C | -0.0000375 | 0.0001057 | 0.7199992 | 0.7226111 | 0.400124 | 0.468850 | NA |
1 | 843405 | rs11516185 | A | G | -0.0001528 | 0.0001312 | 0.2399999 | 0.2443351 | 0.362606 | 0.375399 | NA |
1 | 850218 | rs6664536 | T | A | -0.0001791 | 0.0001054 | 0.0890000 | 0.0893208 | 0.590331 | 0.345248 | NA |
1 | 850371 | rs6679046 | G | T | -0.0001623 | 0.0001060 | 0.1299999 | 0.1257764 | 0.603723 | 0.508786 | NA |
1 | 850780 | rs6657440 | C | T | -0.0001724 | 0.0001060 | 0.1000000 | 0.1038506 | 0.603942 | 0.560304 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51163039 | rs715584 | G | T | -0.0001058 | 0.0001053 | 0.3200000 | 0.3151740 | 0.426975 | 0.473642 | NA |
22 | 51164109 | rs5770995 | G | C | -0.0000700 | 0.0001047 | 0.5000000 | 0.5036875 | 0.452705 | 0.510982 | NA |
22 | 51164115 | rs5770996 | C | T | -0.0000641 | 0.0001046 | 0.5400003 | 0.5403405 | 0.456917 | 0.514776 | NA |
22 | 51164287 | rs6009957 | T | C | -0.0000892 | 0.0001125 | 0.4299995 | 0.4281415 | 0.306541 | 0.415535 | NA |
22 | 51174048 | rs9628245 | G | C | -0.0001226 | 0.0001182 | 0.2999998 | 0.2996310 | 0.380135 | 0.433107 | NA |
22 | 51181919 | rs9616825 | G | C | 0.0001088 | 0.0001192 | 0.3599996 | 0.3612669 | 0.695470 | 0.619409 | NA |
22 | 51186143 | rs2879914 | T | C | -0.0000777 | 0.0001114 | 0.4899999 | 0.4855488 | 0.381825 | 0.273363 | NA |
22 | 51186228 | rs3865766 | C | T | -0.0000528 | 0.0001086 | 0.6300007 | 0.6264733 | 0.451061 | 0.453275 | NA |
22 | 51197266 | rs61290853 | A | G | -0.0000447 | 0.0001121 | 0.6899999 | 0.6900851 | 0.386333 | 0.422923 | NA |
22 | 51212875 | rs2238837 | A | C | -0.0000205 | 0.0001196 | 0.8600001 | 0.8639466 | 0.331457 | 0.372404 | NA |
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