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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_6154_100.vcf.gz --id UKB-b:11085 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_6154_100.txt.gz --cohort_cases 252893 --cohort_controls 204654 --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": "2019-09-13T01:53:58.447624",
"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-11085/mac_discard.txt -Oz /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-11085/UKB-b-11085_raw.vcf.gz; Date=Thu Oct 17 12:24:59 2019",
"bcftools_viewCommand.1": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-b-11085/ukb-b-11085.vcf.gz; Date=Sun May 10 05:05:26 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-11085/UKB-b-11085_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-11085/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:40:18 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-11085/UKB-b-11085_data.vcf.gz ...
Read summary statistics for 9649119 SNPs.
Dropped 12870 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, 1288684 SNPs remain.
After merging with regression SNP LD, 1288684 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0534 (0.002)
Lambda GC: 1.4269
Mean Chi^2: 1.5057
Intercept: 1.0384 (0.0088)
Ratio: 0.0759 (0.0173)
Analysis finished at Thu Oct 17 14:42:01 2019
Total time elapsed: 1.0m:43.03s
{
"af_correlation": 0.9494,
"inflation_factor": 1.3107,
"mean_EFFECT": -0.0001,
"n": "-Inf",
"n_snps": 9851866,
"n_clumped_hits": 31,
"n_p_sig": 7174,
"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": 154087,
"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": 1288684,
"ldsc_nsnp_merge_regression_ld": 1288684,
"ldsc_observed_scale_h2_beta": 0.0534,
"ldsc_observed_scale_h2_se": 0.002,
"ldsc_intercept_beta": 1.0384,
"ldsc_intercept_se": 0.0088,
"ldsc_lambda_gc": 1.4269,
"ldsc_mean_chisq": 1.5057,
"ldsc_ratio": 0.0759
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | TRUE |
n | TRUE |
is_snpid_non_unique | FALSE |
mean_EFFECT_nonfinite | FALSE |
mean_EFFECT_05 | FALSE |
mean_EFFECT_01 | FALSE |
mean_chisq | TRUE |
n_p_sig | TRUE |
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 | 1.000000 | 3 | 58 | 0 | 9636311 | 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 | 9649119 | 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 | 8.626338e+00 | 5.750467e+00 | 1.0000000 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▃▂▂ |
numeric | POS | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 7.883999e+07 | 5.629498e+07 | 828.0000000 | 3.256032e+07 | 6.944278e+07 | 1.145702e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | -7.090000e-05 | 4.635700e-03 | -0.0819540 | -1.704400e-03 | -2.620000e-05 | 1.626500e-03 | 9.499390e-02 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 3.317900e-03 | 2.921200e-03 | 0.0009987 | 1.214400e-03 | 1.990800e-03 | 4.476600e-03 | 5.243710e-02 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 4.578257e-01 | 2.997911e-01 | 0.0000000 | 1.900002e-01 | 4.400003e-01 | 7.199992e-01 | 1.000000e+00 | ▇▆▆▅▆ |
numeric | PVAL_ztest | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 4.578268e-01 | 2.997666e-01 | 0.0000000 | 1.877257e-01 | 4.421466e-01 | 7.176853e-01 | 9.999999e-01 | ▇▆▆▆▆ |
numeric | AF | 0 | 1.000000 | NA | NA | NA | NA | NA | NA | NA | 2.070090e-01 | 2.570439e-01 | 0.0013840 | 1.462300e-02 | 8.298700e-02 | 3.232510e-01 | 9.986160e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 154087 | 0.984031 | NA | NA | NA | NA | NA | NA | NA | 2.093391e-01 | 2.486754e-01 | 0.0000000 | 1.257990e-02 | 1.034350e-01 | 3.254790e-01 | 1.000000e+00 | ▇▂▁▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | 0.0002656 | 0.0018373 | 0.8900000 | 0.8850541 | 0.623783 | 0.7821490 | NA |
1 | 54676 | rs2462492 | C | T | -0.0038444 | 0.0018200 | 0.0350002 | 0.0346659 | 0.400457 | NA | NA |
1 | 86028 | rs114608975 | T | C | 0.0028337 | 0.0029102 | 0.3300000 | 0.3302005 | 0.103543 | 0.0277556 | NA |
1 | 91536 | rs6702460 | G | T | -0.0018719 | 0.0017920 | 0.2999998 | 0.2962220 | 0.456874 | 0.4207270 | NA |
1 | 234313 | rs8179466 | C | T | -0.0006313 | 0.0035330 | 0.8600001 | 0.8581870 | 0.074519 | NA | NA |
1 | 534192 | rs6680723 | C | T | 0.0004638 | 0.0020468 | 0.8200001 | 0.8207228 | 0.240975 | NA | NA |
1 | 546697 | rs12025928 | A | G | -0.0030981 | 0.0025533 | 0.2200002 | 0.2249958 | 0.913488 | NA | NA |
1 | 693731 | rs12238997 | A | G | 0.0009176 | 0.0017148 | 0.5900000 | 0.5925664 | 0.116354 | 0.1417730 | NA |
1 | 705882 | rs72631875 | G | A | 0.0015956 | 0.0025132 | 0.5300002 | 0.5254846 | 0.067296 | 0.0315495 | NA |
1 | 706368 | rs55727773 | A | G | 0.0018879 | 0.0012707 | 0.1400000 | 0.1373748 | 0.515658 | 0.2751600 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219704 | rs147475742 | G | A | -0.0033200 | 0.0026688 | 0.2099999 | 0.2134885 | 0.041945 | 0.0473243 | NA |
22 | 51219766 | rs182321900 | C | T | 0.0016501 | 0.0124486 | 0.8900000 | 0.8945488 | 0.001932 | NA | NA |
22 | 51220146 | rs868950473 | C | T | 0.0043050 | 0.0123325 | 0.7300002 | 0.7270304 | 0.001980 | NA | NA |
22 | 51221190 | rs369304721 | G | A | -0.0026723 | 0.0026641 | 0.3200000 | 0.3158196 | 0.049724 | NA | NA |
22 | 51221731 | rs115055839 | T | C | -0.0022499 | 0.0019929 | 0.2599998 | 0.2589162 | 0.073211 | 0.0625000 | NA |
22 | 51222100 | rs114553188 | G | T | 0.0007851 | 0.0023463 | 0.7400005 | 0.7379190 | 0.054450 | 0.0880591 | NA |
22 | 51223637 | rs375798137 | G | A | 0.0008978 | 0.0023576 | 0.6999999 | 0.7033421 | 0.054078 | 0.0788738 | NA |
22 | 51229805 | rs9616985 | T | C | -0.0023023 | 0.0020001 | 0.2500000 | 0.2497034 | 0.073046 | 0.0730831 | NA |
22 | 51232488 | rs376461333 | A | G | 0.0046488 | 0.0047087 | 0.3200000 | 0.3235049 | 0.020055 | NA | NA |
22 | 51237063 | rs3896457 | T | C | -0.0005275 | 0.0012231 | 0.6700003 | 0.6662940 | 0.297942 | 0.2050720 | NA |
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