manhattan_plot
qq_plot
af_plot
pz_plot
beta_std_plot
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"gwas_harmonisation_command": "--json /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ieu-a-import/processed/ieu-a-106/ieu-a-106_data.json --ref /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/QC/genomes/b37/human_g1k_v37.fasta; 1.1.1",
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"bcftools_viewCommand": "view -h /mnt/storage/private/mrcieu/research/scratch/IGD/data/public/ieu-a-106/ieu-a-106.vcf.gz; Date=Sun May 10 01:36:11 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/dev/ieu-a-import/processed/ieu-a-106/ieu-a-106.vcf.gz \
--ref-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/ \
--out /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ieu-a-import/processed/ieu-a-106/ldsc.txt \
--w-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/
Beginning analysis at Wed Feb 5 10:58:47 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ieu-a-import/processed/ieu-a-106/ieu-a-106.vcf.gz ...
Read summary statistics for 2759235 SNPs.
Reading reference panel LD Score from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/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 /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/[1-22] ...
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1272648 SNPs remain.
After merging with regression SNP LD, 1272648 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.1932 (0.0113)
Lambda GC: 1.006
Mean Chi^2: 1.0594
Intercept: 0.8621 (0.0052)
Ratio < 0 (usually indicates GC correction).
Analysis finished at Wed Feb 5 10:59:21 2020
Total time elapsed: 33.73s{
"af_correlation": 0.9172,
"inflation_factor": 1,
"mean_EFFECT": -0.0003,
"n": 58351.7,
"n_snps": 2759235,
"n_clumped_hits": 9,
"n_p_sig": 401,
"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": 499684,
"n_miss_AF_reference": 27804,
"n_est": 56703.6193,
"ratio_se_n": 0.9858,
"mean_diff": 0,
"ratio_diff": 2.5072,
"sd_y_est1": 1.1237,
"sd_y_est2": 1.1077,
"r2_sum1": 0.0094,
"r2_sum2": 0.0074,
"r2_sum3": 0.0077,
"r2_sum4": 0.0077,
"ldsc_nsnp_merge_refpanel_ld": 1272648,
"ldsc_nsnp_merge_regression_ld": 1272648,
"ldsc_observed_scale_h2_beta": 0.1932,
"ldsc_observed_scale_h2_se": 0.0113,
"ldsc_intercept_beta": 0.8621,
"ldsc_intercept_se": 0.0052,
"ldsc_lambda_gc": 1.006,
"ldsc_mean_chisq": 1.0594,
"ldsc_ratio": -2.3215
}
| name | value |
|---|---|
| name | value |
| af_correlation | FALSE |
| inflation_factor | FALSE |
| n | FALSE |
| 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 betweenAFandAF_reference.inflation_factor(lambda): Genomic inflation factor.mean_EFFECT: Mean ofEFFECTsize.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 below5e-8.n_mono: Number of monomorphic (MAF == 1orMAF == 0) SNPs.n_ns: Number of SNPs with nonsense values:- alleles other than
A, C, G or T. - P-values
< 0or> 1. - negative or infinite standard errors (
<= 0or= Infinity). - infinite beta estimates or allele frequencies
< 0or> 1.
- alleles other than
n_mac: Number of cases whereMAC(2×N×MAF) is less than6.is_snpid_unique:trueif the combination ofIDREFALTis unique and therefore no duplication in snpid.n_miss_<*>: Number ofNAobservations for<*>column.
se_n metrics
n_est: Estimated sample size value, ˆn.ratio_se_n: ratio_se_n=√ˆn√n. We expectratio_se_nto 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.- ^βstdj=√z2j/(z2j+n−2)2×MAFj×(1−MAFj)×sign(zj),
- zj=βjsej,
- and βj is the reported effect size.
ratio_diff: ratio_diff=|mean_diffmean_diff2|, absolute ratio between the mean ofdiffand the mean ofdiff2(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.- mean_diff2=∑j^βstdj−β′jn_snps
- β′j=βj^sd2y
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.- ^sd1y=√n×median(sej)C,
- C=median(1√2×MAFj×(1−MAFj)),
- and sej is the reported standard error.
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.- ^sd2y=median(^sdj),
- ^sdj=βj^βstdj,
r2 metrics
Sum of variance explained, calculated from the clumped top hits sample.
r2_sum<*>:r2statistics under various assumptions1: 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: NOTis_snpid_unique.mean_EFFECT_nonfinite:mean(EFFECT)isNA,NaN, orInf.mean_EFFECT_05:abs(mean(EFFECT))> 0.5.mean_EFFECT_01:abs(mean(EFFECT))> 0.1.mean_chisq:ldsc_mean_chisq> 1.3 orldsc_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<*>> 0.5
Plots
- Manhattan plot
- Red line: −log5×10−810
- Blue line: −log5×10−510
- QQ plot
- AF plot
- P-Z plot
- beta_std plot: Scatter plot between ^βstdj and βj
| skim_type | skim_variable | n_missing | complete_rate | character.min | character.max | character.empty | character.n_unique | character.whitespace | 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 | numeric.mean | numeric.sd | numeric.p0 | numeric.p25 | numeric.p50 | numeric.p75 | numeric.p100 | numeric.hist |
| character | ID | 0 | 1.0000000 | 3 | 42 | 0 | 2759235 | 0 | 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 |
| character | ALT | 0 | 1.0000000 | 1 | 1 | 0 | 4 | 0 | NA | NA | NA | NA | NA | NA | NA | NA |
| numeric | CHROM | 0 | 1.0000000 | NA | NA | NA | NA | NA | 8.615770e+00 | 5.690239e+00 | 1.0000 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.300000e+01 | ▇▅▅▂▂ |
| numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.880929e+07 | 5.590576e+07 | 6689.0000 | 3.245238e+07 | 6.997215e+07 | 1.144397e+08 | 2.492114e+08 | ▇▆▅▂▁ |
| numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | -3.041000e-04 | 5.383510e-02 | -4.0000 | -7.000000e-03 | -1.000000e-04 | 6.800000e-03 | 3.000000e+00 | ▁▁▇▁▁ |
| numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 2.253830e-02 | 5.544740e-02 | 0.0063 | 7.000000e-03 | 8.600000e-03 | 1.400000e-02 | 7.800000e+00 | ▇▁▁▁▁ |
| numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.980096e-01 | 2.907716e-01 | 0.0000 | 2.500000e-01 | 5.000000e-01 | 7.499995e-01 | 1.000000e+00 | ▇▇▇▇▇ |
| numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.979314e-01 | 2.907129e-01 | 0.0000 | 2.433450e-01 | 4.987419e-01 | 7.499161e-01 | 1.000000e+00 | ▇▇▇▇▇ |
| numeric | AF | 499684 | 0.8189049 | NA | NA | NA | NA | NA | 3.565765e-01 | 2.754927e-01 | 0.0083 | 1.167000e-01 | 2.917000e-01 | 5.583000e-01 | 9.917000e-01 | ▇▅▃▂▂ |
| numeric | AF_reference | 27804 | 0.9899233 | NA | NA | NA | NA | NA | 3.528276e-01 | 2.621023e-01 | 0.0000 | 1.319890e-01 | 2.865420e-01 | 5.397360e-01 | 1.000000e+00 | ▇▆▃▂▂ |
| numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | 5.154263e+04 | 1.604436e+04 | 112.0000 | 5.650905e+04 | 5.830810e+04 | 5.832180e+04 | 5.835170e+04 | ▁▁▁▁▇ |
| 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 | 564477 | rs6650104 | A | G | 0.0780 | 0.140 | 0.5700002 | 0.5774298 | NA | 0.0003994 | 1702.56 |
| 1 | 721290 | rs12565286 | G | C | 0.0081 | 0.029 | 0.7800007 | 0.7800067 | NA | 0.0371406 | 21727.00 |
| 1 | 723819 | rs11804171 | T | A | 0.0083 | 0.029 | 0.7800007 | 0.7747197 | NA | 0.1345850 | 21742.00 |
| 1 | 723891 | rs2977670 | G | C | 0.0260 | 0.040 | 0.5199996 | 0.5156922 | NA | 0.7799520 | 11157.00 |
| 1 | 740857 | rs12082473 | G | A | -0.0046 | 0.360 | 0.9900000 | 0.9898051 | NA | 0.0585064 | 2008.00 |
| 1 | 752566 | rs3094315 | G | A | 0.0019 | 0.011 | 0.8600001 | 0.8628658 | NA | 0.7182510 | 36541.80 |
| 1 | 752721 | rs3131972 | A | G | 0.0660 | 0.048 | 0.1700000 | 0.1691314 | NA | 0.6533550 | 1702.75 |
| 1 | 753541 | rs2073813 | G | A | -0.0009 | 0.015 | 0.9500000 | 0.9521556 | NA | 0.3019170 | 23271.00 |
| 1 | 754182 | rs3131969 | A | G | 0.0700 | 0.051 | 0.1700000 | 0.1698926 | NA | 0.6785140 | 1702.92 |
| 1 | 754192 | rs3131968 | A | G | -0.0120 | 0.020 | 0.5300002 | 0.5485062 | NA | 0.6785140 | 14526.10 |
| 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 | 51212875 | rs2238837 | A | C | -0.0033 | 0.0120 | 0.7899998 | 0.7833162 | 0.3917 | 0.3724040 | 28575.90 |
| 22 | 51213613 | rs34726907 | C | T | -0.0880 | 0.0540 | 0.1000000 | 0.1031798 | NA | 0.1727240 | 1873.00 |
| 22 | 51219006 | rs28729663 | G | A | -0.0850 | 0.0480 | 0.0790005 | 0.0765884 | NA | 0.2052720 | 2004.00 |
| 22 | 51229805 | rs9616985 | T | C | -0.0068 | 0.0220 | 0.7600007 | 0.7572524 | 0.0917 | 0.0730831 | 27405.00 |
| 23 | 35921591 | rs2204667 | C | G | -0.0048 | 0.0087 | 0.5800000 | 0.5811374 | 0.1667 | NA | 58318.60 |
| 23 | 51666786 | rs14115 | A | G | 0.0040 | 0.0140 | 0.7800007 | 0.7750970 | 0.0250 | NA | 58137.90 |
| 23 | 70163799 | rs1626496 | A | C | -0.0430 | 0.0120 | 0.0004600 | 0.0003392 | 0.0750 | NA | 58350.90 |
| 23 | 91415872 | rs6562597 | G | A | -0.0027 | 0.0240 | 0.9100000 | 0.9104270 | 0.0083 | 0.0021192 | 56393.40 |
| 23 | 117417363 | rs11541996 | G | A | 0.1800 | 0.2600 | 0.4899999 | 0.4887441 | NA | NA | 1702.87 |
| 23 | 118495837 | rs12882977 | G | A | 0.0005 | 0.0064 | 0.9400001 | 0.9377286 | 0.5167 | 0.2307280 | 58320.20 |
1 564477 rs6650104 A G . PASS . ES:SE:LP:SS:ID 0.078:0.14:0.244125:1702.56:rs6650104
1 721290 rs12565286 G C . PASS . ES:SE:LP:SS:ID 0.0081:0.029:0.107905:21727:rs12565286
1 723819 rs11804171 T A . PASS . ES:SE:LP:SS:ID 0.0083:0.029:0.107905:21742:rs11804171
1 723891 rs2977670 G C . PASS . ES:SE:LP:SS:ID 0.026:0.04:0.283997:11157:rs2977670
1 740857 rs12082473 G A . PASS . ES:SE:LP:SS:ID -0.0046:0.36:0.00436481:2008:rs12082473
1 752566 rs3094315 G A . PASS . ES:SE:LP:SS:ID 0.0019:0.011:0.0655015:36541.8:rs3094315
1 752721 rs3131972 A G . PASS . ES:SE:LP:SS:ID 0.066:0.048:0.769551:1702.75:rs3131972
1 753541 rs2073813 G A . PASS . ES:SE:LP:SS:ID -0.0009:0.015:0.0222764:23271:rs2073813
1 754182 rs3131969 A G . PASS . ES:SE:LP:SS:ID 0.07:0.051:0.769551:1702.92:rs3131969
1 754192 rs3131968 A G . PASS . ES:SE:LP:SS:ID -0.012:0.02:0.275724:14526.1:rs3131968
1 760912 rs1048488 C T . PASS . ES:SE:LP:SS:ID 0.069:0.048:0.823909:1702.94:rs1048488
1 761732 rs2286139 C T . PASS . ES:SE:LP:SS:ID -0.023:0.039:0.251812:2872:rs2286139
1 768448 rs12562034 G A . PASS . ES:SE:LP:SS:ID 0.011:0.022:0.207608:19502.3:rs12562034
1 775659 rs2905035 A G . PASS . ES:SE:LP:SS:ID -0.0031:0.012:0.09691:37796.1:rs2905035
1 776546 rs12124819 A G . PASS . ES:SE:LP:SS:ID 0.02:0.022:0.443698:6467.91:rs12124819
1 777122 rs2980319 A T . PASS . ES:SE:LP:SS:ID -0.0035:0.012:0.113509:37794.9:rs2980319
1 779322 rs4040617 A G . PASS . ES:SE:LP:SS:ID 0.0044:0.012:0.142668:37727.5:rs4040617
1 780785 rs2977612 T A . PASS . ES:SE:LP:SS:ID -0.002:0.012:0.0604807:37795.8:rs2977612
1 784023 rs17160939 A G . PASS . ES:SE:LP:SS:ID 0.12:0.072:1:5685.02:rs17160939
1 785050 rs2905062 G A . PASS . ES:SE:LP:SS:ID -0.001:0.012:0.0315171:37795.7:rs2905062
1 785989 rs2980300 T C . PASS . ES:SE:LP:SS:ID 0.0031:0.012:0.102373:37736.7:rs2980300
1 798026 rs4951864 C T . PASS . ES:SE:LP:SS:ID -0.014:0.023:0.275724:19373.4:rs4951864
1 798801 rs12132517 G A . PASS . ES:SE:LP:SS:ID 0.019:0.023:0.39794:19372.5:rs12132517
1 798959 rs11240777 G A . PASS . ES:SE:LP:SS:ID 0.019:0.015:0.677781:21889.7:rs11240777
1 799463 rs4245756 T C . PASS . ES:SE:LP:SS:ID -0.21:0.41:0.21467:1702.99:rs4245756
1 838555 rs4970383 C A . PASS . ES:SE:LP:SS:ID 0.016:0.041:0.161151:1702.99:rs4970383
1 846808 rs4475691 C T . PASS . ES:SE:LP:SS:ID 0.02:0.028:0.327902:4646.97:rs4475691
1 846864 rs950122 G C . PASS . ES:SE:LP:SS:ID -0.0095:0.073:0.0457575:1700.9:rs950122
1 854250 rs7537756 A G . PASS . ES:SE:LP:SS:ID 0.0079:0.044:0.0655015:1702.96:rs7537756
1 861808 rs13302982 A G . PASS . ES:SE:LP:SS:ID 0.015:0.1:0.0555173:1703:rs13302982
1 863124 rs4040604 G T . PASS . ES:SE:LP:SS:ID -0.0003:0.1:-0:1702.99:rs4040604
1 870645 rs28576697 T C . PASS . ES:SE:LP:SS:ID -0.027:0.039:0.309804:1702.56:rs28576697
1 879317 rs7523549 C T . PASS . ES:SE:LP:SS:ID -0.0081:0.1:0.0268721:1702.91:rs7523549
1 880238 rs3748592 A G . PASS . ES:SE:LP:SS:ID -0.0051:0.078:0.0222764:1702.92:rs3748592
1 880390 rs3748593 C A . PASS . ES:SE:LP:SS:ID -0.016:0.11:0.05061:1703:rs3748593
1 882033 rs2272756 G A . PASS . ES:SE:LP:SS:ID -0.015:0.041:0.142668:1702.98:rs2272756
1 882803 rs2340582 A G . PASS . ES:SE:LP:SS:ID -0.016:0.077:0.0809219:1702.98:rs2340582
1 884815 rs4246503 A G . PASS . ES:SE:LP:SS:ID -0.017:0.077:0.0809219:1702.99:rs4246503
1 886384 rs3748594 G A . PASS . ES:SE:LP:SS:ID -0.0089:0.11:0.0315171:1702.99:rs3748594
1 887162 rs17160698 T C . PASS . ES:SE:LP:SS:ID 0.19:0.26:0.318759:1702.94:rs17160698
1 887560 rs3748595 A C . PASS . ES:SE:LP:SS:ID -0.0096:0.074:0.0457575:1702.93:rs3748595
1 888659 rs3748597 T C . PASS . ES:SE:LP:SS:ID -0.049:0.062:0.366532:2906:rs3748597
1 891945 rs13303106 A G . PASS . ES:SE:LP:SS:ID 0.019:0.037:0.21467:1702.98:rs13303106
1 893981 rs28415373 C T . PASS . ES:SE:LP:SS:ID -0.036:0.2:0.0705811:1702.91:rs28415373
1 894573 rs13303010 G A . PASS . ES:SE:LP:SS:ID -0.0066:0.059:0.0409586:1702.75:rs13303010
1 900505 rs28705211 G C . PASS . ES:SE:LP:SS:ID 0.02:0.024:0.408935:4648.43:rs28705211
1 900730 rs3935066 G A . PASS . ES:SE:LP:SS:ID 0.001:0.061:0.00436481:1702.76:rs3935066
1 903104 rs6696281 C T . PASS . ES:SE:LP:SS:ID 0.011:0.091:0.0457575:1702.98:rs6696281
1 904165 rs28391282 G A . PASS . ES:SE:LP:SS:ID 0.0061:0.33:0.00436481:1703:rs28391282
1 908414 rs28504611 C T . PASS . ES:SE:LP:SS:ID 0.2:0.11:1.19382:1702.88:rs28504611