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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_41246_1390.vcf.gz --id UKB-b:15918 --data /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukbiobank/raw-output/data.batch_41246_1390.txt.gz --cohort_cases 8914 --cohort_controls 435673 --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": "2019-09-13T13:17:42.026065",
"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-15918/mac_discard.txt -Oz /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-15918/UKB-b-15918_raw.vcf.gz; Date=Thu Oct 17 12:32:36 2019",
"bcftools_viewCommand.1": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ukb-b-15918/ukb-b-15918.vcf.gz; Date=Sun May 10 10:48:55 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-15918/UKB-b-15918_data.vcf.gz \
--ref-ld-chr ../reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-15918/ldsc.txt \
--w-ld-chr ../reference/eur_w_ld_chr/
Beginning analysis at Thu Oct 17 14:44:35 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/UKB-b-15918/UKB-b-15918_data.vcf.gz ...
Read summary statistics for 5782811 SNPs.
Dropped 2451 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, 1198505 SNPs remain.
After merging with regression SNP LD, 1198505 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0032 (0.0016)
Lambda GC: 1.0612
Mean Chi^2: 1.0701
Intercept: 1.0403 (0.008)
Ratio: 0.5749 (0.1143)
Analysis finished at Thu Oct 17 14:45:43 2019
Total time elapsed: 1.0m:8.65s
{
"af_correlation": 0.9213,
"inflation_factor": 1.0475,
"mean_EFFECT": 4.7628e-07,
"n": "-Inf",
"n_snps": 9851866,
"n_clumped_hits": 5,
"n_p_sig": 131,
"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": 51674,
"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": 1198505,
"ldsc_nsnp_merge_regression_ld": 1198505,
"ldsc_observed_scale_h2_beta": 0.0032,
"ldsc_observed_scale_h2_se": 0.0016,
"ldsc_intercept_beta": 1.0403,
"ldsc_intercept_se": 0.008,
"ldsc_lambda_gc": 1.0612,
"ldsc_mean_chisq": 1.0701,
"ldsc_ratio": 0.5749
}
name | value |
---|---|
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×N×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, ˆn.ratio_se_n
: ratio_se_n=√ˆn√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
: mean_diff=∑j^βstdj−βjn_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
: ratio_diff=|mean_diffmean_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
: r2=∑j2×β2j×MAFj×(1−MAFj)var1, var1=1.2
: r2=∑j2×β2j×MAFj×(1−MAFj)var2, var2=^sd1y2,3
: r2=∑j2×β2j×MAFj×(1−MAFj)var3, var3=^sd2y2,4
: r2=∑jFjFj+n−2, F=β2jse2j.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 χ2 statistics.ldsc_ratio
: ldsc_intercept_beta−1ldsc_mean_chisq−1, the proportion of the inflation in the mean χ2 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 h2 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 |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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 | 5780376 | 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 | 5782811 | 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 | 8.670417e+00 | 5.762395e+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 | 7.859678e+07 | 5.654471e+07 | 828.0000000 | 3.199487e+07 | 6.903686e+07 | 1.145161e+08 | 2.492385e+08 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 5.000000e-07 | 4.599000e-04 | -0.0034537 | -2.772000e-04 | -5.000000e-07 | 2.782000e-04 | 4.195200e-03 | ▁▂▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.243000e-04 | 1.312000e-04 | 0.0002869 | 3.157000e-04 | 3.741000e-04 | 5.021000e-04 | 1.375900e-03 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.891067e-01 | 2.914282e-01 | 0.0000000 | 2.300001e-01 | 4.899999e-01 | 7.400005e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.891078e-01 | 2.914026e-01 | 0.0000000 | 2.340707e-01 | 4.853826e-01 | 7.415745e-01 | 9.999998e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 3.200923e-01 | 2.508819e-01 | 0.0392650 | 1.066230e-01 | 2.415740e-01 | 4.863110e-01 | 9.607350e-01 | ▇▃▂▂▁ |
numeric | AF_reference | 51674 | 0.9910642 | NA | NA | NA | NA | NA | NA | NA | 3.160371e-01 | 2.445653e-01 | 0.0000000 | 1.150160e-01 | 2.480030e-01 | 4.762380e-01 | 1.000000e+00 | ▇▅▃▂▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
1 | 49298 | rs200943160 | T | C | 0.0000032 | 0.0005278 | 1.0000000 | 0.9952070 | 0.623746 | 0.7821490 | NA |
1 | 54676 | rs2462492 | C | T | -0.0000987 | 0.0005230 | 0.8499999 | 0.8502486 | 0.400427 | NA | NA |
1 | 86028 | rs114608975 | T | C | 0.0003733 | 0.0008361 | 0.6600001 | 0.6552140 | 0.103538 | 0.0277556 | NA |
1 | 91536 | rs6702460 | G | T | -0.0001371 | 0.0005148 | 0.7899998 | 0.7899632 | 0.456859 | 0.4207270 | NA |
1 | 234313 | rs8179466 | C | T | -0.0007273 | 0.0010158 | 0.4700002 | 0.4739739 | 0.074445 | NA | NA |
1 | 534192 | rs6680723 | C | T | -0.0004262 | 0.0005881 | 0.4700002 | 0.4686909 | 0.240915 | NA | NA |
1 | 546697 | rs12025928 | A | G | -0.0007356 | 0.0007338 | 0.3200000 | 0.3161209 | 0.913487 | NA | NA |
1 | 693731 | rs12238997 | A | G | -0.0000694 | 0.0004930 | 0.8900000 | 0.8880508 | 0.116345 | 0.1417730 | NA |
1 | 705882 | rs72631875 | G | A | -0.0012189 | 0.0007223 | 0.0920005 | 0.0915080 | 0.067324 | 0.0315495 | NA |
1 | 706368 | rs55727773 | A | G | -0.0003344 | 0.0003652 | 0.3599996 | 0.3597380 | 0.515712 | 0.2751600 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
22 | 51218377 | rs2519461 | G | C | -0.0003712 | 0.0005703 | 0.5199996 | 0.5151482 | 0.073669 | 0.0826677 | NA |
22 | 51219006 | rs28729663 | G | A | -0.0000623 | 0.0004403 | 0.8900000 | 0.8875541 | 0.138042 | 0.2052720 | NA |
22 | 51219387 | rs9616832 | T | C | -0.0002951 | 0.0005714 | 0.6100002 | 0.6055284 | 0.073796 | 0.0654952 | NA |
22 | 51219704 | rs147475742 | G | A | -0.0006444 | 0.0007658 | 0.4000000 | 0.4000423 | 0.041981 | 0.0473243 | NA |
22 | 51221190 | rs369304721 | G | A | -0.0007308 | 0.0007644 | 0.3400001 | 0.3390304 | 0.049776 | NA | NA |
22 | 51221731 | rs115055839 | T | C | -0.0003650 | 0.0005718 | 0.5199996 | 0.5232522 | 0.073291 | 0.0625000 | NA |
22 | 51222100 | rs114553188 | G | T | 0.0004357 | 0.0006732 | 0.5199996 | 0.5175750 | 0.054522 | 0.0880591 | NA |
22 | 51223637 | rs375798137 | G | A | 0.0004606 | 0.0006765 | 0.5000000 | 0.4959614 | 0.054150 | 0.0788738 | NA |
22 | 51229805 | rs9616985 | T | C | -0.0003432 | 0.0005739 | 0.5500004 | 0.5498848 | 0.073125 | 0.0730831 | NA |
22 | 51237063 | rs3896457 | T | C | -0.0002901 | 0.0003511 | 0.4100001 | 0.4087673 | 0.298132 | 0.2050720 | NA |
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