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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_100012.vcf.gz --id UKB-b:7864 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_100012.txt.gz --cohort_controls 64979 --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": "2019-09-13T15:36:15.758188",
"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-7864/mac_discard.txt -Oz /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-7864/UKB-b-7864_raw.vcf.gz; Date=Thu Oct 17 12:19:52 2019",
"bcftools_viewCommand.1": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-b-7864/ukb-b-7864.vcf.gz; Date=Sun May 10 14:19:24 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-7864/UKB-b-7864_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-7864/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:40:59 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-7864/UKB-b-7864_data.vcf.gz ...
Read summary statistics for 8625788 SNPs.
Dropped 7373 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, 1285750 SNPs remain.
After merging with regression SNP LD, 1285750 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.036 (0.0075)
Lambda GC: 1.0544
Mean Chi^2: 1.0579
Intercept: 1.0124 (0.0063)
Ratio: 0.2147 (0.1082)
Analysis finished at Thu Oct 17 14:42:31 2019
Total time elapsed: 1.0m:31.6s
{
"af_correlation": 0.9462,
"inflation_factor": 1.0475,
"mean_EFFECT": -0.0001,
"n": "-Inf",
"n_snps": 9851866,
"n_clumped_hits": 1,
"n_p_sig": 2,
"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": 83109,
"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": 1285750,
"ldsc_nsnp_merge_regression_ld": 1285750,
"ldsc_observed_scale_h2_beta": 0.036,
"ldsc_observed_scale_h2_se": 0.0075,
"ldsc_intercept_beta": 1.0124,
"ldsc_intercept_se": 0.0063,
"ldsc_lambda_gc": 1.0544,
"ldsc_mean_chisq": 1.0579,
"ldsc_ratio": 0.2142
}
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 | 8618449 | 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 | 8625788 | 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 | 8.650298e+00 | 5.760984e+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 | 7.877027e+07 | 5.637184e+07 | 828.0000000 | 3.238558e+07 | 6.929189e+07 | 1.145689e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -1.047000e-04 | 1.612420e-02 | -0.1745050 | -6.884600e-03 | -7.320000e-05 | 6.702800e-03 | 1.863880e-01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.320840e-02 | 9.017400e-03 | 0.0052452 | 6.176700e-03 | 9.107800e-03 | 1.785610e-02 | 9.043550e-02 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.928644e-01 | 2.902566e-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 | 4.928647e-01 | 2.902302e-01 | 0.0000000 | 2.402431e-01 | 4.902229e-01 | 7.440062e-01 | 9.999999e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.290973e-01 | 2.594859e-01 | 0.0053870 | 2.517900e-02 | 1.138710e-01 | 3.625850e-01 | 9.946120e-01 | ▇▂▁▁▁ |
numeric | AF_reference | 83109 | 0.9903651 | NA | NA | NA | NA | NA | NA | NA | 2.288473e-01 | 2.514568e-01 | 0.0000000 | 2.316290e-02 | 1.303910e-01 | 3.594250e-01 | 1.000000e+00 | ▇▂▂▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 49298 | rs200943160 | T | C | 0.0093261 | 0.0096648 | 0.3300000 | 0.3345718 | 0.623798 | 0.7821490 | NA |
1 | 54676 | rs2462492 | C | T | -0.0063236 | 0.0096366 | 0.5099998 | 0.5116877 | 0.399160 | NA | NA |
1 | 86028 | rs114608975 | T | C | 0.0077754 | 0.0153406 | 0.6100002 | 0.6122570 | 0.103537 | 0.0277556 | NA |
1 | 91536 | rs6702460 | G | T | -0.0031697 | 0.0094792 | 0.7400005 | 0.7380911 | 0.455943 | 0.4207270 | NA |
1 | 234313 | rs8179466 | C | T | 0.0171270 | 0.0187484 | 0.3599996 | 0.3609702 | 0.074448 | NA | NA |
1 | 534192 | rs6680723 | C | T | 0.0029844 | 0.0107957 | 0.7800007 | 0.7822068 | 0.242084 | NA | NA |
1 | 546697 | rs12025928 | A | G | -0.0088230 | 0.0133970 | 0.5099998 | 0.5101668 | 0.912869 | NA | NA |
1 | 693731 | rs12238997 | A | G | -0.0077250 | 0.0090030 | 0.3900004 | 0.3908698 | 0.117299 | 0.1417730 | NA |
1 | 705882 | rs72631875 | G | A | 0.0067128 | 0.0131230 | 0.6100002 | 0.6089815 | 0.067692 | 0.0315495 | NA |
1 | 706368 | rs55727773 | A | G | 0.0079939 | 0.0066822 | 0.2300001 | 0.2315826 | 0.513316 | 0.2751600 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51219006 | rs28729663 | G | A | -0.0091856 | 0.0081268 | 0.2599998 | 0.2583565 | 0.136333 | 0.2052720 | NA |
22 | 51219387 | rs9616832 | T | C | -0.0080990 | 0.0105936 | 0.4400003 | 0.4445562 | 0.071803 | 0.0654952 | NA |
22 | 51219704 | rs147475742 | G | A | -0.0085836 | 0.0140930 | 0.5400003 | 0.5424768 | 0.041187 | 0.0473243 | NA |
22 | 51221190 | rs369304721 | G | A | -0.0043040 | 0.0141924 | 0.7600007 | 0.7616905 | 0.048374 | NA | NA |
22 | 51221731 | rs115055839 | T | C | -0.0080704 | 0.0105959 | 0.4500005 | 0.4462665 | 0.071354 | 0.0625000 | NA |
22 | 51222100 | rs114553188 | G | T | -0.0053240 | 0.0122777 | 0.6600001 | 0.6645565 | 0.054862 | 0.0880591 | NA |
22 | 51223637 | rs375798137 | G | A | -0.0055477 | 0.0123417 | 0.6499995 | 0.6530642 | 0.054481 | 0.0788738 | NA |
22 | 51229805 | rs9616985 | T | C | -0.0091043 | 0.0106286 | 0.3900004 | 0.3916753 | 0.071258 | 0.0730831 | NA |
22 | 51232488 | rs376461333 | A | G | -0.0194853 | 0.0244841 | 0.4299995 | 0.4261280 | 0.020456 | NA | NA |
22 | 51237063 | rs3896457 | T | C | 0.0068653 | 0.0064164 | 0.2800000 | 0.2846359 | 0.298407 | 0.2050720 | NA |
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