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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_20004_1517.vcf.gz --id UKB-b:6354 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_20004_1517.txt.gz --cohort_cases 9236 --cohort_controls 453697 --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": "2019-09-13T01:18:39.939420",
"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-6354/mac_discard.txt -Oz /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-6354/UKB-b-6354_raw.vcf.gz; Date=Thu Oct 17 12:17:55 2019",
"bcftools_viewCommand.1": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-b-6354/ukb-b-6354.vcf.gz; Date=Sat May 9 18:40:32 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-6354/UKB-b-6354_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-6354/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:40:19 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-6354/UKB-b-6354_data.vcf.gz ...
Read summary statistics for 5834973 SNPs.
Dropped 2515 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, 1202641 SNPs remain.
After merging with regression SNP LD, 1202641 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.003 (0.0011)
Lambda GC: 1.0514
Mean Chi^2: 1.062
Intercept: 1.0341 (0.0069)
Ratio: 0.5507 (0.1118)
Analysis finished at Thu Oct 17 14:41:31 2019
Total time elapsed: 1.0m:12.04s
{
"af_correlation": 0.9221,
"inflation_factor": 1.0475,
"mean_EFFECT": 6.1406e-07,
"n": "-Inf",
"n_snps": 9851866,
"n_clumped_hits": 1,
"n_p_sig": 1,
"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": 52274,
"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": 1202641,
"ldsc_nsnp_merge_regression_ld": 1202641,
"ldsc_observed_scale_h2_beta": 0.003,
"ldsc_observed_scale_h2_se": 0.0011,
"ldsc_intercept_beta": 1.0341,
"ldsc_intercept_se": 0.0069,
"ldsc_lambda_gc": 1.0514,
"ldsc_mean_chisq": 1.062,
"ldsc_ratio": 0.55
}
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 | 5832475 | 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 | 5834973 | 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 | 8.669914e+00 | 5.762349e+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 | 7.860032e+07 | 5.653890e+07 | 828.0000000 | 3.199542e+07 | 6.904671e+07 | 1.145336e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 6.000000e-07 | 4.489000e-04 | -0.0037204 | -2.704000e-04 | -8.000000e-07 | 2.711000e-04 | 4.131200e-03 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.180000e-04 | 1.318000e-04 | 0.0002805 | 3.090000e-04 | 3.673000e-04 | 4.959000e-04 | 1.439100e-03 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.915235e-01 | 2.914604e-01 | 0.0000000 | 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 | 4.915222e-01 | 2.914341e-01 | 0.0000000 | 2.363129e-01 | 4.892198e-01 | 7.445244e-01 | 9.999996e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 3.180768e-01 | 2.515207e-01 | 0.0378960 | 1.042710e-01 | 2.387540e-01 | 4.841210e-01 | 9.621040e-01 | ▇▃▂▂▁ |
numeric | AF_reference | 52274 | 0.9910413 | NA | NA | NA | NA | NA | NA | NA | 3.141612e-01 | 2.450515e-01 | 0.0000000 | 1.126200e-01 | 2.454070e-01 | 4.742410e-01 | 1.000000e+00 | ▇▅▃▂▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | -0.0001414 | 0.0005162 | 0.7800007 | 0.7840978 | 0.623763 | 0.7821490 | NA |
1 | 54676 | rs2462492 | C | T | 0.0002056 | 0.0005114 | 0.6899999 | 0.6876963 | 0.400401 | NA | NA |
1 | 86028 | rs114608975 | T | C | 0.0001696 | 0.0008176 | 0.8400000 | 0.8356672 | 0.103556 | 0.0277556 | NA |
1 | 91536 | rs6702460 | G | T | 0.0007219 | 0.0005035 | 0.1499999 | 0.1516498 | 0.456851 | 0.4207270 | NA |
1 | 234313 | rs8179466 | C | T | 0.0020092 | 0.0009928 | 0.0430002 | 0.0429884 | 0.074508 | NA | NA |
1 | 534192 | rs6680723 | C | T | -0.0004411 | 0.0005751 | 0.4400003 | 0.4431141 | 0.240960 | NA | NA |
1 | 546697 | rs12025928 | A | G | 0.0006588 | 0.0007175 | 0.3599996 | 0.3585354 | 0.913473 | NA | NA |
1 | 693731 | rs12238997 | A | G | 0.0006980 | 0.0004820 | 0.1499999 | 0.1475342 | 0.116325 | 0.1417730 | NA |
1 | 705882 | rs72631875 | G | A | -0.0009325 | 0.0007063 | 0.1900002 | 0.1867541 | 0.067285 | 0.0315495 | NA |
1 | 706368 | rs55727773 | A | G | 0.0003023 | 0.0003570 | 0.4000000 | 0.3971497 | 0.515650 | 0.2751600 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51218377 | rs2519461 | G | C | 0.0002152 | 0.0005579 | 0.6999999 | 0.6996814 | 0.073625 | 0.0826677 | NA |
22 | 51219006 | rs28729663 | G | A | 0.0001538 | 0.0004307 | 0.7199992 | 0.7211034 | 0.137953 | 0.2052720 | NA |
22 | 51219387 | rs9616832 | T | C | 0.0002098 | 0.0005591 | 0.7099994 | 0.7075098 | 0.073747 | 0.0654952 | NA |
22 | 51219704 | rs147475742 | G | A | 0.0008935 | 0.0007492 | 0.2300001 | 0.2329904 | 0.041955 | 0.0473243 | NA |
22 | 51221190 | rs369304721 | G | A | -0.0000815 | 0.0007480 | 0.9100000 | 0.9132351 | 0.049731 | NA | NA |
22 | 51221731 | rs115055839 | T | C | 0.0001881 | 0.0005594 | 0.7400005 | 0.7366221 | 0.073238 | 0.0625000 | NA |
22 | 51222100 | rs114553188 | G | T | 0.0001076 | 0.0006586 | 0.8700001 | 0.8701973 | 0.054459 | 0.0880591 | NA |
22 | 51223637 | rs375798137 | G | A | 0.0001035 | 0.0006618 | 0.8800001 | 0.8757714 | 0.054088 | 0.0788738 | NA |
22 | 51229805 | rs9616985 | T | C | 0.0002792 | 0.0005614 | 0.6200004 | 0.6190172 | 0.073073 | 0.0730831 | NA |
22 | 51237063 | rs3896457 | T | C | 0.0004853 | 0.0003434 | 0.1600000 | 0.1575635 | 0.297971 | 0.2050720 | NA |
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