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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/ieu-a-import/processed/ieu-a-1020/ieu-a-1020.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-1020/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 09:02:26 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ieu-a-import/processed/ieu-a-1020/ieu-a-1020.vcf.gz ...
Read summary statistics for 2578062 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, 1138869 SNPs remain.
After merging with regression SNP LD, 1138869 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.0721 (0.1555)
Lambda GC: 1.0265
Mean Chi^2: 1.0286
Intercept: 1.025 (0.0073)
Ratio: 0.8734 (0.2533)
Analysis finished at Wed Feb 5 09:02:57 2020
Total time elapsed: 31.08s
{
"af_correlation": 0.979,
"inflation_factor": 1.0367,
"mean_EFFECT": -0.0001,
"n": 2469,
"n_snps": 2578062,
"n_clumped_hits": 0,
"n_p_sig": 0,
"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": 19411,
"n_est": 2448.9646,
"ratio_se_n": 0.9959,
"mean_diff": -0.0001,
"ratio_diff": 7.4652,
"sd_y_est1": 0.6613,
"sd_y_est2": 0.6586,
"r2_sum1": 0,
"r2_sum2": 0,
"r2_sum3": 0,
"r2_sum4": 0,
"ldsc_nsnp_merge_refpanel_ld": 1138869,
"ldsc_nsnp_merge_regression_ld": 1138869,
"ldsc_observed_scale_h2_beta": 0.0721,
"ldsc_observed_scale_h2_se": 0.1555,
"ldsc_intercept_beta": 1.025,
"ldsc_intercept_se": 0.0073,
"ldsc_lambda_gc": 1.0265,
"ldsc_mean_chisq": 1.0286,
"ldsc_ratio": 0.8741
}
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
(\(2 \times N \times MAF\)) 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 | numeric.mean | numeric.sd | numeric.p0 | numeric.p25 | numeric.p50 | numeric.p75 | numeric.p100 | numeric.hist |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
character | ID | 0 | 1.0000000 | 3 | 42 | 0 | 2578062 | 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 | 8.516211e+00 | 5.637751e+00 | 1.0000000 | 4.000000e+00 | 8.000000e+00 | 1.200000e+01 | 2.300000e+01 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.932376e+07 | 5.562145e+07 | 6689.0000000 | 3.332626e+07 | 7.064748e+07 | 1.146547e+08 | 2.492086e+08 | ▇▇▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | -1.225000e-04 | 3.620360e-02 | -0.4527790 | -1.815890e-02 | -4.820000e-05 | 1.801890e-02 | 3.852080e-01 | ▁▁▇▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 3.083730e-02 | 1.662360e-02 | 0.0163228 | 1.989900e-02 | 2.359050e-02 | 3.444720e-02 | 1.116980e-01 | ▇▂▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.943346e-01 | 2.901662e-01 | 0.0000005 | 2.418332e-01 | 4.922435e-01 | 7.457444e-01 | 9.999999e-01 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.943346e-01 | 2.901662e-01 | 0.0000005 | 2.418331e-01 | 4.922437e-01 | 7.457452e-01 | 9.999999e-01 | ▇▇▇▇▇ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | 3.416883e-01 | 2.773394e-01 | 0.0100002 | 1.017280e-01 | 2.683965e-01 | 5.375318e-01 | 9.900000e-01 | ▇▅▃▂▂ |
numeric | AF_reference | 19411 | 0.9924707 | NA | NA | NA | NA | NA | 3.430599e-01 | 2.689383e-01 | 0.0001997 | 1.134190e-01 | 2.691690e-01 | 5.317490e-01 | 1.000000e+00 | ▇▅▃▂▂ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | 2.469000e+03 | 0.000000e+00 | 2469.0000000 | 2.469000e+03 | 2.469000e+03 | 2.469000e+03 | 2.469000e+03 | ▁▁▇▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 721290 | rs12565286 | G | C | 0.0732684 | 0.0559883 | 0.1906567 | 0.1906571 | 0.0276029 | 0.0371406 | 2469 |
1 | 740857 | rs12082473 | G | A | -0.0498580 | 0.0580071 | 0.3900560 | 0.3900562 | 0.0274006 | 0.0585064 | 2469 |
1 | 752566 | rs3094315 | G | A | 0.0462189 | 0.0210270 | 0.0279434 | 0.0279438 | 0.7432170 | 0.7182510 | 2469 |
1 | 754192 | rs3131968 | A | G | 0.0595149 | 0.0216890 | 0.0060693 | 0.0060693 | 0.6967960 | 0.6785140 | 2469 |
1 | 761732 | rs2286139 | C | T | 0.0524992 | 0.0203066 | 0.0097286 | 0.0097287 | 0.6902330 | 0.6257990 | 2469 |
1 | 777122 | rs2980319 | A | T | 0.0644756 | 0.0222471 | 0.0037536 | 0.0037536 | 0.7769980 | 0.7472040 | 2469 |
1 | 779322 | rs4040617 | A | G | -0.0696964 | 0.0232695 | 0.0027428 | 0.0027428 | 0.2087660 | 0.2264380 | 2469 |
1 | 785050 | rs2905062 | G | A | 0.0530424 | 0.0205935 | 0.0100039 | 0.0100041 | 0.6714540 | 0.6269970 | 2469 |
1 | 785989 | rs2980300 | T | C | 0.0512512 | 0.0201837 | 0.0111094 | 0.0111095 | 0.6629380 | 0.6269970 | 2469 |
1 | 792480 | rs2905036 | C | T | 0.0542852 | 0.0686264 | 0.4289296 | 0.4289294 | 0.9813380 | 0.9768370 | 2469 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51212875 | rs2238837 | A | C | 0.0149721 | 0.0187196 | 0.4238205 | 0.4238216 | 0.3673970 | 0.3724040 | 2469 |
22 | 51213613 | rs34726907 | C | T | -0.0153625 | 0.0281342 | 0.5850352 | 0.5850360 | 0.1313430 | 0.1727240 | 2469 |
22 | 51217134 | rs117417021 | A | G | 0.0165072 | 0.0201206 | 0.4119808 | 0.4119808 | 0.3994350 | 0.2671730 | 2469 |
22 | 51219006 | rs28729663 | G | A | -0.0324486 | 0.0227810 | 0.1543402 | 0.1543391 | 0.2110250 | 0.2052720 | 2469 |
23 | 35921591 | rs2204667 | C | G | -0.0392157 | 0.0292832 | 0.1805095 | 0.1805096 | 0.1200600 | NA | 2469 |
23 | 51115886 | rs17864968 | C | G | -0.0161856 | 0.0668038 | 0.8085586 | 0.8085589 | 0.0205441 | NA | 2469 |
23 | 51666786 | rs14115 | A | G | -0.0174998 | 0.0267761 | 0.5133942 | 0.5133950 | 0.1366080 | NA | 2469 |
23 | 70163799 | rs1626496 | A | C | -0.0503931 | 0.0372241 | 0.1758081 | 0.1758078 | 0.0722227 | NA | 2469 |
23 | 91415872 | rs6562597 | G | A | -0.0748643 | 0.0554515 | 0.1769889 | 0.1769884 | 0.0338732 | 0.0021192 | 2469 |
23 | 118495837 | rs12882977 | G | A | -0.0098779 | 0.0190305 | 0.6037220 | 0.6037222 | 0.3894150 | 0.2307280 | 2469 |
1 721290 rs12565286 G C . PASS AF=0.0276029 ES:SE:LP:AF:SS:ID 0.0732684:0.0559883:0.719748:0.0276029:2469:rs12565286
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1 792480 rs2905036 C T . PASS AF=0.981338 ES:SE:LP:AF:SS:ID 0.0542852:0.0686264:0.367614:0.981338:2469:rs2905036
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1 1018704 rs9442372 A G . PASS AF=0.671797 ES:SE:LP:AF:SS:ID 0.0254117:0.0197144:0.70465:0.671797:2469:rs9442372
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1 1121014 rs3813204 G A . PASS AF=0.261842 ES:SE:LP:AF:SS:ID 0.0548446:0.0239189:1.66052:0.261842:2469:rs3813204
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1 1125553 rs10907174 A T . PASS AF=0.358099 ES:SE:LP:AF:SS:ID 0.0497048:0.0202522:1.85028:0.358099:2469:rs10907174
1 1129672 rs11260554 G T . PASS AF=0.286718 ES:SE:LP:AF:SS:ID 0.0483152:0.021124:1.65398:0.286718:2469:rs11260554
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1 1158277 rs3813199 G A . PASS AF=0.0716707 ES:SE:LP:AF:SS:ID -0.0109804:0.0363485:0.117711:0.0716707:2469:rs3813199
1 1158631 rs6603781 A G . PASS AF=0.925279 ES:SE:LP:AF:SS:ID 0.00773458:0.0354237:0.0824101:0.925279:2469:rs6603781
1 1162435 rs3766186 C A . PASS AF=0.0706432 ES:SE:LP:AF:SS:ID -0.00843364:0.0375203:0.0850467:0.0706432:2469:rs3766186
1 1163804 rs7515488 C T . PASS AF=0.144801 ES:SE:LP:AF:SS:ID -0.0214224:0.0270566:0.368051:0.144801:2469:rs7515488
1 1165310 rs11260562 G A . PASS AF=0.100922 ES:SE:LP:AF:SS:ID -0.0246181:0.0302628:0.380964:0.100922:2469:rs11260562
1 1194804 rs11804831 T C . PASS AF=0.599022 ES:SE:LP:AF:SS:ID 0.00735282:0.021768:0.133401:0.599022:2469:rs11804831
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