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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_5NJ.vcf.gz --id UKB-b:9266 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_41229_5NJ.txt.gz --cohort_cases 2489 --cohort_controls 460521 --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-9266/ukb-b-9266.vcf.gz; Date=Sun May 10 15:05:58 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-9266/UKB-b-9266_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-9266/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:42:23 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-9266/UKB-b-9266_data.vcf.gz ...
Read summary statistics for 3653132 SNPs.
Dropped 611 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, 885888 SNPs remain.
After merging with regression SNP LD, 885888 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: -0.0003 (0.0015)
Lambda GC: 1.1314
Mean Chi^2: 1.126
Intercept: 1.1289 (0.011)
Ratio: 1.0235 (0.0871)
Analysis finished at Thu Oct 17 14:43:09 2019
Total time elapsed: 45.21s
{
"af_correlation": 0.8598,
"inflation_factor": 1.1474,
"mean_EFFECT": 1.0937e-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": 29463,
"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": 885888,
"ldsc_nsnp_merge_regression_ld": 885888,
"ldsc_observed_scale_h2_beta": "NA",
"ldsc_observed_scale_h2_se": "NA",
"ldsc_intercept_beta": 1.1289,
"ldsc_intercept_se": 0.011,
"ldsc_lambda_gc": 1.1314,
"ldsc_mean_chisq": 1.126,
"ldsc_ratio": 1.023
}
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 | 3 | 58 | 0 | 3652524 | 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 | 3653132 | 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 | 8.660966e+00 | 5.771247e+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 | 7.854649e+07 | 5.676473e+07 | 828.0000000 | 3.157479e+07 | 6.887914e+07 | 1.147162e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.000000e-07 | 1.843000e-04 | -0.0011093 | -1.232000e-04 | 2.000000e-07 | 1.232000e-04 | 1.050000e-03 | ▁▁▇▂▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.728000e-04 | 1.960000e-05 | 0.0001464 | 1.557000e-04 | 1.665000e-04 | 1.865000e-04 | 5.353000e-04 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.801249e-01 | 2.925800e-01 | 0.0000010 | 2.200002e-01 | 4.700002e-01 | 7.300002e-01 | 1.000000e+00 | ▇▇▇▆▆ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.801284e-01 | 2.925549e-01 | 0.0000010 | 2.228553e-01 | 4.719621e-01 | 7.329277e-01 | 9.999997e-01 | ▇▇▇▆▆ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.088161e-01 | 2.011508e-01 | 0.1406190 | 2.326740e-01 | 3.671810e-01 | 5.607432e-01 | 8.593810e-01 | ▇▅▃▃▂ |
numeric | AF_reference | 29463 | 0.9919349 | NA | NA | NA | NA | NA | NA | NA | 3.959659e-01 | 2.089461e-01 | 0.0000000 | 2.248400e-01 | 3.616210e-01 | 5.481230e-01 | 1.000000e+00 | ▅▇▆▃▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | -0.0001108 | 0.0002693 | 0.6800001 | 0.6806152 | 0.623765 | 0.782149 | NA |
1 | 54676 | rs2462492 | C | T | -0.0002960 | 0.0002668 | 0.2700001 | 0.2672246 | 0.400401 | NA | NA |
1 | 91536 | rs6702460 | G | T | 0.0001164 | 0.0002627 | 0.6600001 | 0.6576640 | 0.456846 | 0.420727 | NA |
1 | 534192 | rs6680723 | C | T | 0.0002406 | 0.0003000 | 0.4199997 | 0.4225515 | 0.240959 | NA | NA |
1 | 706368 | rs55727773 | A | G | 0.0001320 | 0.0001863 | 0.4799997 | 0.4786337 | 0.515645 | 0.275160 | NA |
1 | 729679 | rs4951859 | C | G | 0.0004897 | 0.0002179 | 0.0250000 | 0.0246230 | 0.843204 | 0.639976 | NA |
1 | 752566 | rs3094315 | G | A | 0.0004669 | 0.0002110 | 0.0269998 | 0.0269344 | 0.838945 | 0.718251 | NA |
1 | 752721 | rs3131972 | A | G | 0.0004643 | 0.0002108 | 0.0280001 | 0.0276272 | 0.838573 | 0.653355 | NA |
1 | 754503 | rs3115859 | G | A | 0.0004801 | 0.0002102 | 0.0219999 | 0.0223836 | 0.838026 | 0.663938 | NA |
1 | 754964 | rs3131966 | C | T | 0.0004741 | 0.0002108 | 0.0250000 | 0.0245206 | 0.838657 | 0.663339 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51182485 | rs6009961 | A | G | 0.0001440 | 0.0001759 | 0.4100001 | 0.4131631 | 0.715502 | 0.6383790 | NA |
22 | 51186143 | rs2879914 | T | C | 0.0002296 | 0.0001631 | 0.1600000 | 0.1591992 | 0.381825 | 0.2733630 | NA |
22 | 51186228 | rs3865766 | C | T | 0.0001783 | 0.0001590 | 0.2599998 | 0.2622107 | 0.451061 | 0.4532750 | NA |
22 | 51192586 | rs5771006 | G | A | -0.0000843 | 0.0002142 | 0.6899999 | 0.6939717 | 0.167627 | 0.0848642 | NA |
22 | 51193227 | rs34608236 | T | G | -0.0005406 | 0.0002190 | 0.0140001 | 0.0135528 | 0.168490 | 0.0692891 | NA |
22 | 51197266 | rs61290853 | A | G | 0.0001092 | 0.0001641 | 0.5099998 | 0.5060379 | 0.386333 | 0.4229230 | NA |
22 | 51198027 | rs34939255 | A | G | -0.0000942 | 0.0001858 | 0.6100002 | 0.6123032 | 0.254562 | 0.0984425 | NA |
22 | 51211106 | rs9628250 | T | C | -0.0000990 | 0.0001842 | 0.5900000 | 0.5911598 | 0.271547 | 0.1671330 | NA |
22 | 51212875 | rs2238837 | A | C | 0.0000584 | 0.0001750 | 0.7400005 | 0.7384862 | 0.331457 | 0.3724040 | NA |
22 | 51237063 | rs3896457 | T | C | 0.0001709 | 0.0001792 | 0.3400001 | 0.3402757 | 0.297974 | 0.2050720 | NA |
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