manhattan_plot
qq_plot
af_plot
pz_plot
beta_std_plot
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"Gwas2VCF_command": "--data /data/cromwell-executions/qc/0cddccd3-66b2-4eb5-bf41-8a330bdbbfab/call-vcf/inputs/-261044473/upload.txt.gz --id ieu-b-4838 --json /data/cromwell-executions/qc/0cddccd3-66b2-4eb5-bf41-8a330bdbbfab/call-vcf/inputs/-261044473/ieu-b-4838_data.json --ref /data/cromwell-executions/qc/0cddccd3-66b2-4eb5-bf41-8a330bdbbfab/call-vcf/inputs/1899004205/human_g1k_v37.fasta --dbsnp /data/cromwell-executions/qc/0cddccd3-66b2-4eb5-bf41-8a330bdbbfab/call-vcf/inputs/-307190728/dbsnp.v153.b37.vcf.gz --out /data/igd/ieu-b-4838/ieu-b-4838.vcf.gz --alias alias.txt; 1.3.0",
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}
*********************************************************************
* 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 /data/cromwell-executions/qc/0cddccd3-66b2-4eb5-bf41-8a330bdbbfab/call-ldsc/inputs/-261044473/ieu-b-4838.vcf.gz \
--ref-ld-chr /data/ref/eur_w_ld_chr/ \
--out /data/igd/ieu-b-4838/ldsc.txt \
--w-ld-chr /data/ref/eur_w_ld_chr/
Beginning analysis at Wed Jan 5 12:41:27 2022
Reading summary statistics from /data/cromwell-executions/qc/0cddccd3-66b2-4eb5-bf41-8a330bdbbfab/call-ldsc/inputs/-261044473/ieu-b-4838.vcf.gz ...
Read summary statistics for 6719230 SNPs.
Dropped 18738 SNPs with duplicated rs numbers.
Reading reference panel LD Score from /data/ref/eur_w_ld_chr/[1-22] ... (ldscore_fromlist)
Read reference panel LD Scores for 1290028 SNPs.
Removing partitioned LD Scores with zero variance.
Reading regression weight LD Score from /data/ref/eur_w_ld_chr/[1-22] ... (ldscore_fromlist)
Read regression weight LD Scores for 1290028 SNPs.
After merging with reference panel LD, 1186489 SNPs remain.
After merging with regression SNP LD, 1186489 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.2412 (0.0262)
Lambda GC: 1.1325
Mean Chi^2: 1.1468
Intercept: 1.0429 (0.0073)
Ratio: 0.2921 (0.0496)
Analysis finished at Wed Jan 5 12:43:07 2022
Total time elapsed: 1.0m:40.03s{
"af_correlation": "NA",
"inflation_factor": 1.1197,
"mean_EFFECT": -0,
"n": 22593,
"n_snps": 6719302,
"n_clumped_hits": 3,
"n_p_sig": 8,
"n_mono": 0,
"n_ns": 0,
"n_mac": 0,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 6719302,
"n_miss_AF_reference": 53316,
"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": 1186489,
"ldsc_nsnp_merge_regression_ld": 1186489,
"ldsc_observed_scale_h2_beta": 0.2412,
"ldsc_observed_scale_h2_se": 0.0262,
"ldsc_intercept_beta": 1.0429,
"ldsc_intercept_se": 0.0073,
"ldsc_lambda_gc": 1.1325,
"ldsc_mean_chisq": 1.1468,
"ldsc_ratio": 0.2922
}
| name | value |
|---|---|
| name | value |
| af_correlation | NA |
| inflation_factor | FALSE |
| n | FALSE |
| is_snpid_non_unique | TRUE |
| 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 | 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 | 45 | 0.9999933 | 3 | 58 | 0 | 6719206 | 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 | AF | 6719302 | 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 | 8.660922e+00 | 5.761272e+00 | 1.0000e+00 | 4.000000e+00 | 8.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▅▅▂▂ |
| numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 7.862500e+07 | 5.646681e+07 | 8.2800e+02 | 3.212334e+07 | 6.907324e+07 | 1.145122e+08 | 2.492385e+08 | ▇▆▅▂▁ |
| numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | -1.890000e-05 | 1.887290e-02 | -1.7880e-01 | -9.900000e-03 | 0.000000e+00 | 9.800000e-03 | 1.679000e-01 | ▁▁▇▁▁ |
| numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.609430e-02 | 8.095100e-03 | 8.8000e-03 | 9.900000e-03 | 1.240000e-02 | 2.030000e-02 | 5.020000e-02 | ▇▂▁▁▁ |
| numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.812381e-01 | 2.937850e-01 | 0.0000e+00 | 2.224001e-01 | 4.753998e-01 | 7.352008e-01 | 1.000000e+00 | ▇▇▇▇▇ |
| numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.812402e-01 | 2.937904e-01 | 0.0000e+00 | 2.224649e-01 | 4.753789e-01 | 7.352262e-01 | 1.000000e+00 | ▇▇▇▇▇ |
| numeric | AF_reference | 53316 | 0.9920652 | NA | NA | NA | NA | NA | NA | NA | 2.828646e-01 | 2.508425e-01 | 1.9970e-04 | 7.727640e-02 | 2.032750e-01 | 4.369010e-01 | 1.000000e+00 | ▇▃▂▂▁ |
| numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.062050e+04 | 2.225197e+03 | 1.3564e+04 | 1.873700e+04 | 2.167800e+04 | 2.259300e+04 | 2.259300e+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 | 49298 | rs200943160 | T | C | 0.0023 | 0.0116 | 0.8442001 | 0.8428292 | NA | 0.7821490 | 16660 |
| 1 | 54676 | rs2462492 | C | T | -0.0043 | 0.0123 | 0.7290998 | 0.7266438 | NA | NA | 16660 |
| 1 | 86028 | rs114608975 | T | C | -0.0089 | 0.0223 | 0.6902001 | 0.6898172 | NA | 0.0277556 | 16165 |
| 1 | 91536 | rs6702460 | G | T | -0.0126 | 0.0121 | 0.2971002 | 0.2977260 | NA | 0.4207270 | 16660 |
| 1 | 234313 | rs8179466 | C | T | -0.0273 | 0.0269 | 0.3109997 | 0.3101679 | NA | NA | 16165 |
| 1 | 534192 | rs6680723 | C | T | 0.0174 | 0.0141 | 0.2167999 | 0.2171870 | NA | NA | 16660 |
| 1 | 546697 | rs12025928 | A | G | 0.0140 | 0.0198 | 0.4812004 | 0.4795225 | NA | NA | 16165 |
| 1 | 693731 | rs12238997 | A | G | -0.0187 | 0.0166 | 0.2597000 | 0.2599514 | NA | 0.1417730 | 16806 |
| 1 | 705882 | rs72631875 | G | A | -0.0135 | 0.0230 | 0.5578995 | 0.5572329 | NA | 0.0315495 | 16165 |
| 1 | 706368 | rs55727773 | A | G | -0.0098 | 0.0109 | 0.3654997 | 0.3686087 | NA | 0.2751600 | 16660 |
| 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 | 0.0174 | 0.0185 | 0.3483999 | 0.3469404 | NA | 0.0826677 | 19232 |
| 22 | 51219006 | rs28729663 | G | A | 0.0036 | 0.0143 | 0.8010000 | 0.8012357 | NA | 0.2052720 | 19106 |
| 22 | 51219387 | rs9616832 | T | C | 0.0117 | 0.0199 | 0.5554002 | 0.5565728 | NA | 0.0654952 | 16660 |
| 22 | 51219704 | rs147475742 | G | A | 0.0127 | 0.0247 | 0.6065003 | 0.6071331 | NA | 0.0473243 | 18737 |
| 22 | 51221190 | rs369304721 | G | A | 0.0232 | 0.0221 | 0.2941000 | 0.2938221 | NA | NA | 18737 |
| 22 | 51221731 | rs115055839 | T | C | 0.0114 | 0.0200 | 0.5675002 | 0.5686777 | NA | 0.0625000 | 16660 |
| 22 | 51222100 | rs114553188 | G | T | 0.0020 | 0.0221 | 0.9277001 | 0.9278917 | NA | 0.0880591 | 18737 |
| 22 | 51223637 | rs375798137 | G | A | 0.0024 | 0.0222 | 0.9132000 | 0.9139099 | NA | 0.0788738 | 18737 |
| 22 | 51229805 | rs9616985 | T | C | 0.0133 | 0.0200 | 0.5068005 | 0.5060505 | NA | 0.0730831 | 16660 |
| 22 | 51237063 | rs3896457 | T | C | -0.0080 | 0.0112 | 0.4772995 | 0.4750505 | NA | 0.2050720 | 17301 |
1 49298 rs10399793 T C . PASS . ES:SE:LP:SS:ID 0.0023:0.0116:0.0735546:16660:rs10399793
1 54676 rs2462492 C T . PASS . ES:SE:LP:SS:ID -0.0043:0.0123:0.137213:16660:rs2462492
1 86028 rs114608975 T C . PASS . ES:SE:LP:SS:ID -0.0089:0.0223:0.161025:16165:rs114608975
1 91536 rs1251109649 G T . PASS . ES:SE:LP:SS:ID -0.0126:0.0121:0.527097:16660:rs1251109649
1 234313 rs8179466 C T . PASS . ES:SE:LP:SS:ID -0.0273:0.0269:0.50724:16165:rs8179466
1 534192 rs6680723 C T . PASS . ES:SE:LP:SS:ID 0.0174:0.0141:0.663941:16660:rs6680723
1 546697 rs12025928 A G . PASS . ES:SE:LP:SS:ID 0.014:0.0198:0.317674:16165:rs12025928
1 693731 rs12238997 A G . PASS . ES:SE:LP:SS:ID -0.0187:0.0166:0.585528:16806:rs12238997
1 705882 rs72631875 G A . PASS . ES:SE:LP:SS:ID -0.0135:0.023:0.253444:16165:rs72631875
1 706368 rs963699400 A G . PASS . ES:SE:LP:SS:ID -0.0098:0.0109:0.437113:16660:rs963699400
1 714596 rs149887893 T C . PASS . ES:SE:LP:SS:ID 0.0098:0.0311:0.12332:16165:rs149887893
1 715265 rs12184267 C T . PASS . ES:SE:LP:SS:ID 0.0213:0.0299:0.322667:16165:rs12184267
1 715367 rs12184277 A G . PASS . ES:SE:LP:SS:ID 0.0187:0.0299:0.273925:16165:rs12184277
1 717485 rs12184279 C A . PASS . ES:SE:LP:SS:ID 0.0221:0.0301:0.334044:16165:rs12184279
1 720381 rs116801199 G T . PASS . ES:SE:LP:SS:ID 0.0207:0.0301:0.308388:16165:rs116801199
1 721290 rs12565286 G C . PASS . ES:SE:LP:SS:ID 0.0219:0.0299:0.334513:16165:rs12565286
1 722670 rs116030099 T C . PASS . ES:SE:LP:SS:ID -0.0061:0.0194:0.121766:16165:rs116030099
1 723891 rs2977670 G C . PASS . ES:SE:LP:SS:ID -0.0118:0.0273:0.176526:16165:rs2977670
1 726794 rs28454925 C G . PASS . ES:SE:LP:SS:ID 0.0285:0.0299:0.46916:16165:rs28454925
1 729632 rs116720794 C T . PASS . ES:SE:LP:SS:ID 0.0322:0.0298:0.553774:16165:rs116720794
1 729679 rs4951859 C G . PASS . ES:SE:LP:SS:ID 0.0072:0.0145:0.207328:17301:rs4951859
1 730087 rs148120343 T C . PASS . ES:SE:LP:SS:ID 0.0187:0.0237:0.366835:16165:rs148120343
1 731718 rs58276399 T C . PASS . ES:SE:LP:SS:ID -0.0133:0.0159:0.394695:17432:rs58276399
1 732989 rs369030935 C T . PASS . ES:SE:LP:SS:ID -0.0403:0.0385:0.529149:16165:rs369030935
1 734349 rs141242758 T C . PASS . ES:SE:LP:SS:ID -0.0148:0.0159:0.453334:17432:rs141242758
1 736289 rs1254887344 T A . PASS . ES:SE:LP:SS:ID -0.0082:0.0156:0.221632:17301:rs1254887344
1 752478 rs146277091 G A . PASS . ES:SE:LP:SS:ID 0.0209:0.0296:0.318036:16165:rs146277091
1 752566 rs3094315 G A . PASS . ES:SE:LP:SS:ID 0.0065:0.0139:0.195588:18496:rs3094315
1 752721 rs3131972 A G . PASS . ES:SE:LP:SS:ID 0.004:0.014:0.111147:17927:rs3131972
1 753405 rs3115860 C A . PASS . ES:SE:LP:SS:ID 0.0079:0.0151:0.22062:17432:rs3115860
1 753541 rs1388595942 G A . PASS . ES:SE:LP:SS:ID -0.0081:0.0155:0.219539:17432:rs1388595942
1 754063 rs12184312 G T . PASS . ES:SE:LP:SS:ID 0.0198:0.0297:0.297311:16165:rs12184312
1 754105 rs12184325 C T . PASS . ES:SE:LP:SS:ID 0.0192:0.0298:0.284164:16165:rs12184325
1 754182 rs3131969 A G . PASS . ES:SE:LP:SS:ID 0.0054:0.0151:0.141944:17432:rs3131969
1 754192 rs3131968 A G . PASS . ES:SE:LP:SS:ID 0.0054:0.0151:0.141944:17432:rs3131968
1 754211 rs12184313 G A . PASS . ES:SE:LP:SS:ID 0.0219:0.0296:0.337053:16165:rs12184313
1 754334 rs3131967 T C . PASS . ES:SE:LP:SS:ID 0.0052:0.0151:0.136558:17432:rs3131967
1 754503 rs3115859 G A . PASS . ES:SE:LP:SS:ID 0.0035:0.014:0.094366:17927:rs3115859
1 754629 rs10454459 A G . PASS . ES:SE:LP:SS:ID 0.0207:0.0296:0.31399:16165:rs10454459
1 754964 rs3131966 C T . PASS . ES:SE:LP:SS:ID 0.0052:0.014:0.148497:17927:rs3131966
1 755775 rs3131965 A G . PASS . ES:SE:LP:SS:ID 0.0074:0.014:0.223154:17927:rs3131965
1 755890 rs1280367067 A T . PASS . ES:SE:LP:SS:ID 0.0081:0.0151:0.228339:17432:rs1280367067
1 756604 rs3131962 A G . PASS . ES:SE:LP:SS:ID 0.0079:0.0151:0.223371:17432:rs3131962
1 757640 rs3115853 G A . PASS . ES:SE:LP:SS:ID 0.0054:0.015:0.143694:17432:rs3115853
1 757734 rs1557551770 C T . PASS . ES:SE:LP:SS:ID 0.0082:0.0151:0.233513:17432:rs1557551770
1 757936 rs1360886751 C A . PASS . ES:SE:LP:SS:ID 0.0082:0.0151:0.233513:17432:rs1360886751
1 758144 rs3131956 A G . PASS . ES:SE:LP:SS:ID 0.0082:0.0151:0.233513:17432:rs3131956
1 758626 rs3131954 C T . PASS . ES:SE:LP:SS:ID 0.008:0.0151:0.225994:17432:rs3131954
1 759036 rs114525117 G A . PASS . ES:SE:LP:SS:ID 0.0175:0.03:0.252045:16165:rs114525117
1 760912 rs1048488 C T . PASS . ES:SE:LP:SS:ID 0.0054:0.014:0.156331:17927:rs1048488