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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_20003_1140865354.vcf.gz --id UKB-b:12861 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_20003_1140865354.txt.gz --cohort_cases 2470 --cohort_controls 460463 --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": "2019-09-12T17:53:42.358136",
"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-12861/mac_discard.txt -Oz /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-12861/UKB-b-12861_raw.vcf.gz; Date=Thu Oct 17 12:27:56 2019",
"bcftools_viewCommand.1": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-b-12861/ukb-b-12861.vcf.gz; Date=Sat May 9 13:14:44 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-12861/UKB-b-12861_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-12861/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:42:07 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-12861/UKB-b-12861_data.vcf.gz ...
Read summary statistics for 3637658 SNPs.
Dropped 604 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, 882809 SNPs remain.
After merging with regression SNP LD, 882809 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0046 (0.0011)
Lambda GC: 1.0452
Mean Chi^2: 1.0408
Intercept: 0.9941 (0.0088)
Ratio < 0 (usually indicates GC correction).
Analysis finished at Thu Oct 17 14:42:56 2019
Total time elapsed: 49.53s
{
"af_correlation": 0.859,
"inflation_factor": 1.0475,
"mean_EFFECT": -1.3319e-06,
"n": "-Inf",
"n_snps": 9851866,
"n_clumped_hits": 1,
"n_p_sig": 20,
"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": 29336,
"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": 882809,
"ldsc_nsnp_merge_regression_ld": 882809,
"ldsc_observed_scale_h2_beta": 0.0046,
"ldsc_observed_scale_h2_se": 0.0011,
"ldsc_intercept_beta": 0.9941,
"ldsc_intercept_se": 0.0088,
"ldsc_lambda_gc": 1.0452,
"ldsc_mean_chisq": 1.0408,
"ldsc_ratio": -0.1446
}
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 | 3637057 | 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 | 3637658 | 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 | 8.661548e+00 | 5.771654e+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 | 7.854194e+07 | 5.675598e+07 | 828.0000000 | 3.157784e+07 | 6.887881e+07 | 1.147126e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -1.300000e-06 | 1.766000e-04 | -0.0008976 | -1.187000e-04 | -2.200000e-06 | 1.164000e-04 | 9.654000e-04 | ▁▂▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.723000e-04 | 1.940000e-05 | 0.0001461 | 1.554000e-04 | 1.661000e-04 | 1.858000e-04 | 5.344000e-04 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.938091e-01 | 2.912391e-01 | 0.0000000 | 2.399999e-01 | 4.899999e-01 | 7.499995e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.938100e-01 | 2.912172e-01 | 0.0000000 | 2.387089e-01 | 4.914837e-01 | 7.467490e-01 | 9.999988e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.094518e-01 | 2.005919e-01 | 0.1417010 | 2.338120e-01 | 3.680625e-01 | 5.610490e-01 | 8.582990e-01 | ▇▅▃▃▂ |
numeric | AF_reference | 29336 | 0.9919355 | NA | NA | NA | NA | NA | NA | NA | 3.965268e-01 | 2.085626e-01 | 0.0000000 | 2.256390e-01 | 3.624200e-01 | 5.485220e-01 | 1.000000e+00 | ▅▇▆▃▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | 0.0002030 | 0.0002689 | 0.4500005 | 0.4502256 | 0.623763 | 0.782149 | NA |
1 | 54676 | rs2462492 | C | T | -0.0002934 | 0.0002664 | 0.2700001 | 0.2708106 | 0.400401 | NA | NA |
1 | 91536 | rs6702460 | G | T | 0.0002026 | 0.0002623 | 0.4400003 | 0.4397916 | 0.456851 | 0.420727 | NA |
1 | 534192 | rs6680723 | C | T | -0.0001431 | 0.0002996 | 0.6300007 | 0.6329469 | 0.240960 | NA | NA |
1 | 706368 | rs55727773 | A | G | 0.0001100 | 0.0001860 | 0.5500004 | 0.5542251 | 0.515650 | 0.275160 | NA |
1 | 729679 | rs4951859 | C | G | -0.0000027 | 0.0002176 | 0.9900000 | 0.9902264 | 0.843212 | 0.639976 | NA |
1 | 752566 | rs3094315 | G | A | -0.0000359 | 0.0002107 | 0.8600001 | 0.8647795 | 0.838951 | 0.718251 | NA |
1 | 752721 | rs3131972 | A | G | -0.0000210 | 0.0002105 | 0.9199999 | 0.9204722 | 0.838580 | 0.653355 | NA |
1 | 754503 | rs3115859 | G | A | -0.0000155 | 0.0002099 | 0.9400001 | 0.9410416 | 0.838033 | 0.663938 | NA |
1 | 754964 | rs3131966 | C | T | -0.0000064 | 0.0002105 | 0.9800000 | 0.9757460 | 0.838664 | 0.663339 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51182485 | rs6009961 | A | G | 0.0001512 | 0.0001756 | 0.3900004 | 0.3891499 | 0.715505 | 0.6383790 | NA |
22 | 51186143 | rs2879914 | T | C | 0.0001902 | 0.0001628 | 0.2399999 | 0.2427583 | 0.381826 | 0.2733630 | NA |
22 | 51186228 | rs3865766 | C | T | 0.0001052 | 0.0001587 | 0.5099998 | 0.5073994 | 0.451063 | 0.4532750 | NA |
22 | 51192586 | rs5771006 | G | A | 0.0000873 | 0.0002138 | 0.6800001 | 0.6830567 | 0.167620 | 0.0848642 | NA |
22 | 51193227 | rs34608236 | T | G | -0.0000624 | 0.0002186 | 0.7800007 | 0.7753524 | 0.168489 | 0.0692891 | NA |
22 | 51197266 | rs61290853 | A | G | -0.0000235 | 0.0001639 | 0.8900000 | 0.8859634 | 0.386333 | 0.4229230 | NA |
22 | 51198027 | rs34939255 | A | G | 0.0000979 | 0.0001855 | 0.5999997 | 0.5975934 | 0.254557 | 0.0984425 | NA |
22 | 51211106 | rs9628250 | T | C | 0.0000261 | 0.0001839 | 0.8900000 | 0.8872175 | 0.271547 | 0.1671330 | NA |
22 | 51212875 | rs2238837 | A | C | 0.0001283 | 0.0001747 | 0.4600002 | 0.4627807 | 0.331455 | 0.3724040 | NA |
22 | 51237063 | rs3896457 | T | C | 0.0001660 | 0.0001789 | 0.3500000 | 0.3534028 | 0.297971 | 0.2050720 | NA |
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