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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 /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/folkersen-pqtl-gwas-import/processed/PROT-b-81/PROT-b-81.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/folkersen-pqtl-gwas-import/processed/PROT-b-81/ldsc.txt \
--w-ld-chr /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/reference/eur_w_ld_chr/
Beginning analysis at Mon Oct 28 22:10:17 2019
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/folkersen-pqtl-gwas-import/processed/PROT-b-81/PROT-b-81.vcf.gz ...
Read summary statistics for 4217519 SNPs.
Dropped 1 SNPs with duplicated rs numbers.
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, 625178 SNPs remain.
After merging with regression SNP LD, 625178 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.1745 (0.1801)
Lambda GC: 1.003
Mean Chi^2: 1.0078
Intercept: 0.9941 (0.0109)
Ratio < 0 (usually indicates GC correction).
Analysis finished at Mon Oct 28 22:11:00 2019
Total time elapsed: 42.56s
{
"af_correlation": 0.956,
"inflation_factor": 1.0103,
"mean_EFFECT": 0.0041,
"n": "-Inf",
"n_snps": 4217519,
"n_clumped_hits": 0,
"n_p_sig": 9,
"n_mono": 417,
"n_ns": 261122,
"n_mac": 0,
"is_snpid_unique": false,
"n_miss_EFFECT": 0,
"n_miss_SE": 0,
"n_miss_PVAL": 0,
"n_miss_AF": 0,
"n_miss_AF_reference": 311294,
"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": 625178,
"ldsc_nsnp_merge_regression_ld": 625178,
"ldsc_observed_scale_h2_beta": 0.1745,
"ldsc_observed_scale_h2_se": 0.1801,
"ldsc_intercept_beta": 0.9941,
"ldsc_intercept_se": 0.0109,
"ldsc_lambda_gc": 1.003,
"ldsc_mean_chisq": 1.0078,
"ldsc_ratio": -0.7564
}
name | value |
---|---|
af_correlation | FALSE |
inflation_factor | FALSE |
n | TRUE |
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 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 | 4217516 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | REF | 0 | 1.0000000 | 1 | 3 | 0 | 80 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
character | ALT | 0 | 1.0000000 | 1 | 3 | 0 | 80 | 0 | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
logical | N | 4217519 | 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 | 9.844030e+00 | 5.113267e+00 | 1.0000 | 5.000000e+00 | 9.000000e+00 | 1.300000e+01 | 2.200000e+01 | ▇▇▇▅▃ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 7.057353e+07 | 4.563585e+07 | 34918.0000 | 3.236389e+07 | 6.477455e+07 | 1.035942e+08 | 1.977961e+08 | ▇▇▆▃▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.058700e-03 | 2.794070e-01 | -15.2037 | -3.650000e-02 | 4.000000e-04 | 3.770000e-02 | 8.204900e+00 | ▁▁▁▇▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 1.318065e-01 | 2.360986e-01 | 0.0233 | 3.390000e-02 | 4.740000e-02 | 1.090000e-01 | 3.319800e+00 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.987661e-01 | 2.885233e-01 | 0.0000 | 2.498999e-01 | 4.978001e-01 | 7.481006e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 4.985788e-01 | 2.886386e-01 | 0.0000 | 2.494989e-01 | 4.976503e-01 | 7.480081e-01 | 1.000000e+00 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | NA | NA | 2.803965e-01 | 2.812576e-01 | 0.0000 | 3.810000e-02 | 1.804000e-01 | 4.641000e-01 | 1.000000e+00 | ▇▃▂▂▁ |
numeric | AF_reference | 311294 | 0.9261903 | NA | NA | NA | NA | NA | NA | NA | 2.547631e-01 | 2.537602e-01 | 0.0000 | 3.913740e-02 | 1.693290e-01 | 4.075480e-01 | 1.000000e+00 | ▇▃▂▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 104917910 | rs113234741 | G | A | 0.4183 | 0.5733 | 0.4666003 | 0.4656131 | 0.0156 | NA | NA |
2 | 18642530 | rs111710788 | G | C | 0.0825 | 0.0815 | 0.3117001 | 0.3114090 | 0.9708 | NA | NA |
2 | 161008726 | rs77875881 | C | T | 0.0807 | 0.0506 | 0.1109001 | 0.1107432 | 0.1037 | 0.0095847 | NA |
3 | 60363 | rs141398405 | A | G | 0.0526 | 0.0716 | 0.4626004 | 0.4625607 | 0.0556 | 0.0257588 | NA |
3 | 60596 | rs13067307 | C | A | -0.0082 | 0.0268 | 0.7589008 | 0.7596274 | 0.4852 | 0.5591050 | NA |
3 | 60648 | rs138886950 | A | G | -0.1274 | 0.0961 | 0.1852000 | 0.1849383 | 0.0470 | 0.0325479 | NA |
3 | 61044 | rs9755941 | T | C | 0.0090 | 0.0256 | 0.7243993 | 0.7251664 | 0.5048 | 0.5976440 | NA |
3 | 61113 | rs9756992 | A | T | 0.0019 | 0.0246 | 0.9387000 | 0.9384360 | 0.4468 | 0.5710860 | NA |
3 | 61466 | rs13081384 | G | C | 0.0310 | 0.0290 | 0.2846997 | 0.2850852 | 0.2629 | 0.1725240 | NA |
3 | 61495 | rs13060385 | A | G | 0.0027 | 0.0273 | 0.9213001 | 0.9212168 | 0.4530 | 0.4826280 | NA |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51163039 | rs715584 | G | T | 0.0573 | 0.0301 | 0.0569600 | 0.0569552 | 0.4131 | 0.4736420 | NA |
22 | 51163138 | rs715586 | C | T | 0.0607 | 0.0361 | 0.0931001 | 0.0926774 | 0.1273 | 0.0902556 | NA |
22 | 51163910 | rs192700691 | C | T | 0.1128 | 0.1074 | 0.2933999 | 0.2935897 | 0.0304 | 0.0295527 | NA |
22 | 51164109 | rs5770995 | G | C | 0.0422 | 0.0283 | 0.1360000 | 0.1359179 | 0.4411 | 0.5109820 | NA |
22 | 51164115 | rs5770996 | C | T | 0.0426 | 0.0284 | 0.1340001 | 0.1336144 | 0.4446 | 0.5147760 | NA |
22 | 51164287 | rs6009957 | T | C | 0.0148 | 0.0274 | 0.5882000 | 0.5890964 | 0.3052 | 0.4155350 | NA |
22 | 51165664 | rs8137951 | G | A | 0.0154 | 0.0266 | 0.5627001 | 0.5626247 | 0.2954 | 0.4063500 | NA |
22 | 51171693 | rs756638 | G | A | 0.0084 | 0.0387 | 0.8275000 | 0.8281661 | 0.3046 | 0.3049120 | NA |
22 | 51175626 | rs3810648 | A | G | 0.0887 | 0.0604 | 0.1418999 | 0.1419568 | 0.0735 | 0.1084270 | NA |
22 | 51178090 | rs2285395 | G | A | 0.0840 | 0.0573 | 0.1424000 | 0.1426568 | 0.0481 | 0.0666933 | NA |
1 104917910 rs113234741 G A . PASS AF=0.0156 ES:SE:LP:AF:ID 0.4183:0.5733:0.331055:0.0156:rs113234741
2 18642530 rs111710788 G C . PASS AF=0.9708 ES:SE:LP:AF:ID 0.0825:0.0815:0.506263:0.9708:rs111710788
2 161008726 rs77875881 C T . PASS AF=0.1037 ES:SE:LP:AF:ID 0.0807:0.0506:0.955068:0.1037:rs77875881
3 60363 rs141398405 A G . PASS AF=0.0556 ES:SE:LP:AF:ID 0.0526:0.0716:0.334794:0.0556:rs141398405
3 60596 rs13067307 C A . PASS AF=0.4852 ES:SE:LP:AF:ID -0.0082:0.0268:0.119815:0.4852:rs13067307
3 60648 rs138886950 A G . PASS AF=0.047 ES:SE:LP:AF:ID -0.1274:0.0961:0.732359:0.047:rs138886950
3 61044 rs9755941 T C . PASS AF=0.5048 ES:SE:LP:AF:ID 0.009:0.0256:0.140022:0.5048:rs9755941
3 61113 rs9756992 A T . PASS AF=0.4468 ES:SE:LP:AF:ID 0.0019:0.0246:0.0274732:0.4468:rs9756992
3 61466 rs13081384 G C . PASS AF=0.2629 ES:SE:LP:AF:ID 0.031:0.029:0.545613:0.2629:rs13081384
3 61495 rs13060385 A G . PASS AF=0.453 ES:SE:LP:AF:ID 0.0027:0.0273:0.0355989:0.453:rs13060385
3 61662 rs73009205 T C . PASS AF=0.0581 ES:SE:LP:AF:ID 0.0505:0.0682:0.337714:0.0581:rs73009205
3 61762 rs62240674 T A . PASS AF=0.3163 ES:SE:LP:AF:ID 0.0154:0.026:0.257118:0.3163:rs62240674
3 62226 rs9799162 C T . PASS AF=0.3198 ES:SE:LP:AF:ID 0.0172:0.0261:0.29243:0.3198:rs9799162
3 62309 rs9681823 T G . PASS AF=0.2467 ES:SE:LP:AF:ID 0.0171:0.0339:0.212115:0.2467:rs9681823
3 62337 rs180933565 G A . PASS AF=0.002 ES:SE:LP:AF:ID -0.6497:0.4567:0.809949:0.002:rs180933565
3 62425 rs73009208 A C . PASS AF=0.0582 ES:SE:LP:AF:ID 0.0501:0.0679:0.336582:0.0582:rs73009208
3 62437 rs9682412 A T . PASS AF=0.7703 ES:SE:LP:AF:ID 0.0292:0.0317:0.446845:0.7703:rs9682412
3 62614 rs9799274 G C . PASS AF=0.316 ES:SE:LP:AF:ID 0.0153:0.0259:0.256725:0.316:rs9799274
3 62746 rs13073823 C G . PASS AF=0.1151 ES:SE:LP:AF:ID -0.0391:0.0405:0.474566:0.1151:rs13073823
3 62759 rs34815673 A C . PASS AF=0.1151 ES:SE:LP:AF:ID -0.0391:0.0405:0.474696:0.1151:rs34815673
3 62886 rs58497705 A T . PASS AF=0.3197 ES:SE:LP:AF:ID 0.0169:0.0261:0.287687:0.3197:rs58497705
3 62971 rs9682645 C A . PASS AF=0.3262 ES:SE:LP:AF:ID 0.0194:0.0276:0.315873:0.3262:rs9682645
3 62981 rs59670147 C T . PASS AF=0.3197 ES:SE:LP:AF:ID 0.0168:0.0261:0.284916:0.3197:rs59670147
3 63411 rs13072188 A C . PASS AF=0.4445 ES:SE:LP:AF:ID 0.0017:0.0241:0.0246601:0.4445:rs13072188
3 63989 3_63989_C_CAT CAT C . PASS AF=0.641 ES:SE:LP:AF:ID -0.0123:0.031:0.159518:0.641:3_63989_C_CAT
3 64165 rs9311287 C A . PASS AF=0.1836 ES:SE:LP:AF:ID -0.0433:0.0365:0.62764:0.1836:rs9311287
3 64189 rs113405791 C T . PASS AF=0.0583 ES:SE:LP:AF:ID 0.0499:0.0673:0.338471:0.0583:rs113405791
3 64221 rs9311316 C T . PASS AF=0.7677 ES:SE:LP:AF:ID 0.0282:0.0317:0.427709:0.7677:rs9311316
3 64492 rs34166985 T A . PASS AF=0.2673 ES:SE:LP:AF:ID 0.0295:0.0281:0.533281:0.2673:rs34166985
3 64940 rs142582846 G A . PASS AF=0.0453 ES:SE:LP:AF:ID -0.1324:0.0982:0.750068:0.0453:rs142582846
3 65592 rs150394040 T C . PASS AF=0.0442 ES:SE:LP:AF:ID -0.1345:0.098:0.769551:0.0442:rs150394040
3 65982 rs73009220 G A . PASS AF=0.2977 ES:SE:LP:AF:ID 0.0391:0.0293:0.740884:0.2977:rs73009220
3 66083 rs9713920 T C . PASS AF=0.1463 ES:SE:LP:AF:ID -0.0635:0.0398:0.95546:0.1463:rs9713920
3 66164 rs35007339 C G . PASS AF=0.6275 ES:SE:LP:AF:ID 0.0536:0.0281:1.24911:0.6275:rs35007339
3 66342 rs28716985 T G . PASS AF=0.3315 ES:SE:LP:AF:ID 0.0164:0.0267:0.268653:0.3315:rs28716985
3 66519 3_66519_G_GA GA G . PASS AF=0.9529 ES:SE:LP:AF:ID 0.1246:0.0935:0.738499:0.9529:3_66519_G_GA
3 66866 rs9683305 C T . PASS AF=0.3009 ES:SE:LP:AF:ID 0.0361:0.029:0.671824:0.3009:rs9683305
3 66894 rs9681213 G A . PASS AF=0.3018 ES:SE:LP:AF:ID 0.0361:0.0289:0.674484:0.3018:rs9681213
3 67116 rs9681345 G A . PASS AF=0.3018 ES:SE:LP:AF:ID 0.0361:0.0289:0.674484:0.3018:rs9681345
3 67176 rs150705890 C T . PASS AF=0.0096 ES:SE:LP:AF:ID 0.0046:0.1337:0.0120657:0.0096:rs150705890
3 67279 rs67010098 G A . PASS AF=0.2406 ES:SE:LP:AF:ID 0.0485:0.0297:0.9897:0.2406:rs67010098
3 67801 rs9681389 G C . PASS AF=0.4932 ES:SE:LP:AF:ID -0.0088:0.0266:0.130358:0.4932:rs9681389
3 67818 rs62240679 T G . PASS AF=0.3244 ES:SE:LP:AF:ID 0.0156:0.0265:0.254613:0.3244:rs62240679
3 68079 rs12631621 G C . PASS AF=0.1186 ES:SE:LP:AF:ID -0.0347:0.04:0.413863:0.1186:rs12631621
3 68204 rs67723366 G C . PASS AF=0.1225 ES:SE:LP:AF:ID -0.03:0.0389:0.356942:0.1225:rs67723366
3 68426 rs71306185 C T . PASS AF=0.1071 ES:SE:LP:AF:ID -0.043:0.0428:0.501689:0.1071:rs71306185
3 68528 rs113565524 C G . PASS AF=0.0231 ES:SE:LP:AF:ID -0.033:0.1075:0.119701:0.0231:rs113565524
3 69244 rs13089679 T C . PASS AF=0.2871 ES:SE:LP:AF:ID 0.0279:0.0263:0.538802:0.2871:rs13089679
3 69456 rs112317660 G T . PASS AF=0.0237 ES:SE:LP:AF:ID -0.0302:0.1074:0.108686:0.0237:rs112317660
3 70895 rs9682794 T C . PASS AF=0.3279 ES:SE:LP:AF:ID 0.0177:0.0268:0.293709:0.3279:rs9682794