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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_41229_5HX.vcf.gz --id UKB-b:16102 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_41229_5HX.txt.gz --cohort_cases 1528 --cohort_controls 461482 --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",
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"bcftools_viewCommand.1": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-b-16102/ukb-b-16102.vcf.gz; Date=Sat May 9 17:47:09 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-16102/UKB-b-16102_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-16102/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:44:45 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-16102/UKB-b-16102_data.vcf.gz ...
Read summary statistics for 2545060 SNPs.
Dropped 301 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, 643363 SNPs remain.
After merging with regression SNP LD, 643363 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: -0.001 (0.0012)
Lambda GC: 1.0488
Mean Chi^2: 1.0505
Intercept: 1.0613 (0.0089)
Ratio: 1.2139 (0.1764)
Analysis finished at Thu Oct 17 14:45:19 2019
Total time elapsed: 34.37s
{
"af_correlation": 0.7738,
"inflation_factor": 1.0475,
"mean_EFFECT": -1.951e-06,
"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": 20196,
"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": 643363,
"ldsc_nsnp_merge_regression_ld": 643363,
"ldsc_observed_scale_h2_beta": "NA",
"ldsc_observed_scale_h2_se": "NA",
"ldsc_intercept_beta": 1.0613,
"ldsc_intercept_se": 0.0089,
"ldsc_lambda_gc": 1.0488,
"ldsc_mean_chisq": 1.0505,
"ldsc_ratio": 1.2139
}
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 | 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 | 1.0000000 | 4 | 58 | 0 | 2544762 | 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 | 2545060 | 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 | 8.657347e+00 | 5.766648e+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 | 7.853560e+07 | 5.661811e+07 | 5687.0000000 | 3.168129e+07 | 6.894543e+07 | 1.147353e+08 | 2.491917e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -2.000000e-06 | 1.303000e-04 | -0.0006518 | -8.950000e-05 | -2.100000e-06 | 8.540000e-05 | 6.676000e-04 | ▁▂▇▂▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.270000e-04 | 7.100000e-06 | 0.0001150 | 1.209000e-04 | 1.249000e-04 | 1.319000e-04 | 2.493000e-04 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.923456e-01 | 2.901660e-01 | 0.0000008 | 2.399999e-01 | 4.899999e-01 | 7.400005e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.923480e-01 | 2.901420e-01 | 0.0000008 | 2.395103e-01 | 4.897153e-01 | 7.434490e-01 | 9.999991e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.517328e-01 | 1.538633e-01 | 0.2290580 | 3.164750e-01 | 4.286930e-01 | 5.749300e-01 | 7.709420e-01 | ▇▆▅▅▃ |
numeric | AF_reference | 20196 | 0.9920646 | NA | NA | NA | NA | NA | NA | NA | 4.335710e-01 | 1.778428e-01 | 0.0001997 | 2.927320e-01 | 4.171330e-01 | 5.636980e-01 | 1.000000e+00 | ▂▇▇▃▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | -0.0000542 | 0.0002116 | 0.8000000 | 0.7980085 | 0.623765 | 0.7821490 | NA |
1 | 54676 | rs2462492 | C | T | 0.0000570 | 0.0002097 | 0.7899998 | 0.7858694 | 0.400401 | NA | NA |
1 | 91536 | rs6702460 | G | T | 0.0002079 | 0.0002064 | 0.3100002 | 0.3138767 | 0.456846 | 0.4207270 | NA |
1 | 534192 | rs6680723 | C | T | 0.0003105 | 0.0002358 | 0.1900002 | 0.1879246 | 0.240959 | NA | NA |
1 | 706368 | rs55727773 | A | G | 0.0001222 | 0.0001464 | 0.4000000 | 0.4038394 | 0.515645 | 0.2751600 | NA |
1 | 763394 | rs369924889 | G | A | 0.0001425 | 0.0001716 | 0.4100001 | 0.4063656 | 0.706753 | 0.6176120 | NA |
1 | 768253 | rs2977608 | A | C | 0.0000905 | 0.0001401 | 0.5199996 | 0.5181983 | 0.761297 | 0.4894170 | NA |
1 | 776546 | rs12124819 | A | G | -0.0000819 | 0.0001565 | 0.5999997 | 0.6005465 | 0.265385 | 0.0756789 | NA |
1 | 814495 | rs74461805 | C | A | 0.0003776 | 0.0002007 | 0.0599998 | 0.0599670 | 0.340396 | NA | NA |
1 | 830181 | rs28444699 | A | G | -0.0002747 | 0.0001343 | 0.0409996 | 0.0407969 | 0.697255 | 0.6912940 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51180501 | rs5770999 | T | C | -0.0000837 | 0.0001378 | 0.5400003 | 0.5436378 | 0.713656 | 0.6369810 | NA |
22 | 51181919 | rs9616825 | G | C | -0.0000445 | 0.0001371 | 0.7499995 | 0.7453992 | 0.695470 | 0.6194090 | NA |
22 | 51182485 | rs6009961 | A | G | -0.0000896 | 0.0001382 | 0.5199996 | 0.5166023 | 0.715502 | 0.6383790 | NA |
22 | 51186143 | rs2879914 | T | C | -0.0000209 | 0.0001282 | 0.8700001 | 0.8703723 | 0.381825 | 0.2733630 | NA |
22 | 51186228 | rs3865766 | C | T | 0.0000788 | 0.0001249 | 0.5300002 | 0.5279826 | 0.451061 | 0.4532750 | NA |
22 | 51197266 | rs61290853 | A | G | 0.0001433 | 0.0001290 | 0.2700001 | 0.2663759 | 0.386333 | 0.4229230 | NA |
22 | 51198027 | rs34939255 | A | G | -0.0001231 | 0.0001460 | 0.4000000 | 0.3990182 | 0.254562 | 0.0984425 | NA |
22 | 51211106 | rs9628250 | T | C | -0.0001484 | 0.0001447 | 0.3100002 | 0.3053423 | 0.271547 | 0.1671330 | NA |
22 | 51212875 | rs2238837 | A | C | 0.0000440 | 0.0001375 | 0.7499995 | 0.7489127 | 0.331457 | 0.3724040 | NA |
22 | 51237063 | rs3896457 | T | C | -0.0000025 | 0.0001408 | 0.9900000 | 0.9858778 | 0.297974 | 0.2050720 | NA |
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