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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-1004/ieu-a-1004.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-1004/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 11:33:51 2020
Reading summary statistics from /mnt/storage/private/mrcieu/research/scratch/IGD/data/dev/ieu-a-import/processed/ieu-a-1004/ieu-a-1004.vcf.gz ...
Read summary statistics for 2415893 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, 1146515 SNPs remain.
After merging with regression SNP LD, 1146515 SNPs remain.
Using two-step estimator with cutoff at 30.
Total Observed scale h2: 0.1893 (0.0137)
Lambda GC: 0.977
Mean Chi^2: 1.2923
Intercept: 1.0368 (0.0096)
Ratio: 0.1259 (0.0329)
Analysis finished at Wed Feb 5 11:34:20 2020
Total time elapsed: 28.93s
{
"af_correlation": 0.9152,
"inflation_factor": 1.0966,
"mean_EFFECT": 0,
"n": 69360,
"n_snps": 2415893,
"n_clumped_hits": 42,
"n_p_sig": 1208,
"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": 19654,
"n_est": 44460.8974,
"ratio_se_n": 0.8006,
"mean_diff": -0,
"ratio_diff": 44.6001,
"sd_y_est1": 4.6286,
"sd_y_est2": 3.7058,
"r2_sum1": 0.637,
"r2_sum2": 0.0297,
"r2_sum3": 0.0464,
"r2_sum4": 0.0469,
"ldsc_nsnp_merge_refpanel_ld": 1146515,
"ldsc_nsnp_merge_regression_ld": 1146515,
"ldsc_observed_scale_h2_beta": 0.1893,
"ldsc_observed_scale_h2_se": 0.0137,
"ldsc_intercept_beta": 1.0368,
"ldsc_intercept_se": 0.0096,
"ldsc_lambda_gc": 0.977,
"ldsc_mean_chisq": 1.2923,
"ldsc_ratio": 0.1259
}
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 | TRUE |
miss_EFFECT | FALSE |
miss_SE | FALSE |
miss_PVAL | FALSE |
ldsc_ratio | FALSE |
ldsc_intercept_beta | FALSE |
n_clumped_hits | FALSE |
r2_sum1 | TRUE |
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 | 2415893 | 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 | 8.584573e+00 | 5.655200e+00 | 1.0000e+00 | 4.000000e+00 | 8.000000e+00 | 1.200000e+01 | 23.00 | ▇▅▅▂▂ |
numeric | POS | 0 | 1.0000000 | NA | NA | NA | NA | NA | 7.884366e+07 | 5.565313e+07 | 1.1543e+04 | 3.268972e+07 | 7.025702e+07 | 1.143281e+08 | 249210707.00 | ▇▆▅▂▁ |
numeric | EFFECT | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.020000e-05 | 3.794100e-02 | -5.2000e-01 | -2.000000e-02 | 0.000000e+00 | 2.000000e-02 | 0.88 | ▁▇▁▁▁ |
numeric | SE | 0 | 1.0000000 | NA | NA | NA | NA | NA | 3.174310e-02 | 1.682670e-02 | 2.0000e-02 | 2.000000e-02 | 3.000000e-02 | 4.000000e-02 | 0.21 | ▇▁▁▁▁ |
numeric | PVAL | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.856034e-01 | 2.933971e-01 | 0.0000e+00 | 2.300001e-01 | 4.799997e-01 | 7.400005e-01 | 1.00 | ▇▇▇▇▇ |
numeric | PVAL_ztest | 0 | 1.0000000 | NA | NA | NA | NA | NA | 4.815687e-01 | 3.094341e-01 | 0.0000e+00 | 1.824224e-01 | 5.049851e-01 | 7.388827e-01 | 1.00 | ▇▆▃▇▆ |
numeric | AF | 0 | 1.0000000 | NA | NA | NA | NA | NA | 3.616448e-01 | 2.720218e-01 | 1.0000e-02 | 1.200000e-01 | 3.000000e-01 | 5.600000e-01 | 0.99 | ▇▅▃▃▂ |
numeric | AF_reference | 19654 | 0.9918647 | NA | NA | NA | NA | NA | 3.641544e-01 | 2.541254e-01 | 1.9970e-04 | 1.503590e-01 | 3.033150e-01 | 5.479230e-01 | 1.00 | ▇▆▅▃▂ |
numeric | N | 0 | 1.0000000 | NA | NA | NA | NA | NA | 6.936000e+04 | 0.000000e+00 | 6.9360e+04 | 6.936000e+04 | 6.936000e+04 | 6.936000e+04 | 69360.00 | ▁▁▇▁▁ |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
1 | 752566 | rs3094315 | G | A | 0.01 | 0.05 | 0.8300000 | 0.8414806 | 0.83 | 0.718251 | 69360 |
1 | 777122 | rs2980319 | A | T | 0.02 | 0.06 | 0.6700003 | 0.7388827 | 0.87 | 0.747204 | 69360 |
1 | 779322 | rs4040617 | A | G | -0.03 | 0.06 | 0.6300007 | 0.6170751 | 0.13 | 0.226438 | 69360 |
1 | 780785 | rs2977612 | T | A | 0.03 | 0.06 | 0.6600001 | 0.6170751 | 0.86 | 0.669329 | 69360 |
1 | 785050 | rs2905062 | G | A | 0.04 | 0.06 | 0.4899999 | 0.5049851 | 0.86 | 0.626997 | 69360 |
1 | 785989 | rs2980300 | T | C | 0.03 | 0.06 | 0.5900000 | 0.6170751 | 0.85 | 0.626997 | 69360 |
1 | 990380 | rs3121561 | C | T | -0.02 | 0.03 | 0.5400003 | 0.5049851 | 0.29 | 0.343450 | 69360 |
1 | 998501 | rs3813193 | G | C | -0.04 | 0.04 | 0.2599998 | 0.3173105 | 0.17 | 0.206669 | 69360 |
1 | 1003629 | rs4075116 | C | T | -0.01 | 0.03 | 0.6600001 | 0.7388827 | 0.73 | 0.720647 | 69360 |
1 | 1005806 | rs3934834 | C | T | -0.03 | 0.03 | 0.4199997 | 0.3173105 | 0.16 | 0.223442 | 69360 |
CHROM | POS | ID | REF | ALT | EFFECT | SE | PVAL | PVAL_ztest | AF | AF_reference | N |
---|---|---|---|---|---|---|---|---|---|---|---|
22 | 51175626 | rs3810648 | A | G | -0.04 | 0.05 | 0.3800004 | 0.4237108 | 0.07 | 0.1084270 | 69360 |
22 | 51178090 | rs2285395 | G | A | -0.04 | 0.05 | 0.3800004 | 0.4237108 | 0.07 | 0.0666933 | 69360 |
22 | 51196164 | rs8136603 | A | T | -0.06 | 0.06 | 0.2700001 | 0.3173105 | 0.07 | 0.1427720 | 69360 |
22 | 51222100 | rs114553188 | G | T | -0.01 | 0.08 | 0.9000000 | 0.9005236 | 0.07 | 0.0880591 | 69360 |
22 | 51223637 | rs375798137 | G | A | -0.02 | 0.08 | 0.8300000 | 0.8025873 | 0.07 | 0.0788738 | 69360 |
23 | 35921591 | rs2204667 | C | G | -0.06 | 0.04 | 0.1400000 | 0.1336144 | 0.17 | NA | 69360 |
23 | 51666786 | rs14115 | A | G | 0.10 | 0.05 | 0.0500000 | 0.0455003 | 0.02 | NA | 69360 |
23 | 70163799 | rs1626496 | A | C | 0.03 | 0.05 | 0.5300002 | 0.5485062 | 0.07 | NA | 69360 |
23 | 91415872 | rs6562597 | G | A | 0.08 | 0.11 | 0.4500005 | 0.4670589 | 0.01 | 0.0021192 | 69360 |
23 | 118495837 | rs12882977 | G | A | 0.05 | 0.02 | 0.0460002 | 0.0124193 | 0.52 | 0.2307280 | 69360 |
1 752566 rs3094315 G A . PASS AF=0.83 ES:SE:LP:AF:SS:ID 0.01:0.05:0.0809219:0.83:69360:rs3094315
1 777122 rs2980319 A T . PASS AF=0.87 ES:SE:LP:AF:SS:ID 0.02:0.06:0.173925:0.87:69360:rs2980319
1 779322 rs4040617 A G . PASS AF=0.13 ES:SE:LP:AF:SS:ID -0.03:0.06:0.200659:0.13:69360:rs4040617
1 780785 rs2977612 T A . PASS AF=0.86 ES:SE:LP:AF:SS:ID 0.03:0.06:0.180456:0.86:69360:rs2977612
1 785050 rs2905062 G A . PASS AF=0.86 ES:SE:LP:AF:SS:ID 0.04:0.06:0.309804:0.86:69360:rs2905062
1 785989 rs2980300 T C . PASS AF=0.85 ES:SE:LP:AF:SS:ID 0.03:0.06:0.229148:0.85:69360:rs2980300
1 990380 rs3121561 C T . PASS AF=0.29 ES:SE:LP:AF:SS:ID -0.02:0.03:0.267606:0.29:69360:rs3121561
1 998501 rs3813193 G C . PASS AF=0.17 ES:SE:LP:AF:SS:ID -0.04:0.04:0.585027:0.17:69360:rs3813193
1 1003629 rs4075116 C T . PASS AF=0.73 ES:SE:LP:AF:SS:ID -0.01:0.03:0.180456:0.73:69360:rs4075116
1 1005806 rs3934834 C T . PASS AF=0.16 ES:SE:LP:AF:SS:ID -0.03:0.03:0.376751:0.16:69360:rs3934834
1 1017170 rs3766193 C G . PASS AF=0.55 ES:SE:LP:AF:SS:ID 0:0.02:0.05061:0.55:69360:rs3766193
1 1017197 rs3766192 C T . PASS AF=0.55 ES:SE:LP:AF:SS:ID 0:0.02:0.05061:0.55:69360:rs3766192
1 1017587 rs3766191 C T . PASS AF=0.15 ES:SE:LP:AF:SS:ID -0.04:0.04:0.522879:0.15:69360:rs3766191
1 1018562 rs9442371 C T . PASS AF=0.56 ES:SE:LP:AF:SS:ID 0.01:0.02:0.091515:0.56:69360:rs9442371
1 1018704 rs9442372 A G . PASS AF=0.57 ES:SE:LP:AF:SS:ID 0.01:0.02:0.113509:0.57:69360:rs9442372
1 1021346 rs10907177 A G . PASS AF=0.15 ES:SE:LP:AF:SS:ID -0.03:0.04:0.431798:0.15:69360:rs10907177
1 1021415 rs3737728 A G . PASS AF=0.72 ES:SE:LP:AF:SS:ID 0:0.03:0.0268721:0.72:69360:rs3737728
1 1021583 rs10907178 A C . PASS AF=0.15 ES:SE:LP:AF:SS:ID -0.03:0.04:0.318759:0.15:69360:rs10907178
1 1021695 rs9442398 A G . PASS AF=0.72 ES:SE:LP:AF:SS:ID 0:0.03:0.0705811:0.72:69360:rs9442398
1 1022037 rs6701114 C T . PASS AF=0.56 ES:SE:LP:AF:SS:ID 0.01:0.02:0.251812:0.56:69360:rs6701114
1 1026707 rs4074137 C A . PASS AF=0.6 ES:SE:LP:AF:SS:ID 0.04:0.03:0.823909:0.6:69360:rs4074137
1 1030565 rs6687776 C T . PASS AF=0.16 ES:SE:LP:AF:SS:ID -0.02:0.03:0.21467:0.16:69360:rs6687776
1 1030633 rs6678318 G A . PASS AF=0.16 ES:SE:LP:AF:SS:ID -0.04:0.05:0.337242:0.16:69360:rs6678318
1 1031540 rs9651273 A G . PASS AF=0.73 ES:SE:LP:AF:SS:ID 0.03:0.04:0.431798:0.73:69360:rs9651273
1 1036959 rs11579015 T C . PASS AF=0.11 ES:SE:LP:AF:SS:ID -0.02:0.04:0.283997:0.11:69360:rs11579015
1 1040026 rs6671356 T C . PASS AF=0.15 ES:SE:LP:AF:SS:ID -0.03:0.03:0.443698:0.15:69360:rs6671356
1 1046164 rs6666280 C T . PASS AF=0.14 ES:SE:LP:AF:SS:ID -0.03:0.03:0.49485:0.14:69360:rs6666280
1 1048955 rs4970405 A G . PASS AF=0.11 ES:SE:LP:AF:SS:ID -0.04:0.04:0.552842:0.11:69360:rs4970405
1 1049950 rs12726255 A G . PASS AF=0.15 ES:SE:LP:AF:SS:ID -0.03:0.03:0.468521:0.15:69360:rs12726255
1 1053452 rs4970409 G A . PASS AF=0.11 ES:SE:LP:AF:SS:ID -0.03:0.04:0.387216:0.11:69360:rs4970409
1 1060608 rs17160824 G A . PASS AF=0.12 ES:SE:LP:AF:SS:ID -0.03:0.04:0.443698:0.12:69360:rs17160824
1 1061115 rs17160826 T C . PASS AF=0.11 ES:SE:LP:AF:SS:ID -0.04:0.04:0.468521:0.11:69360:rs17160826
1 1061152 rs12748370 T C . PASS AF=0.11 ES:SE:LP:AF:SS:ID -0.03:0.04:0.420216:0.11:69360:rs12748370
1 1061166 rs11807848 T C . PASS AF=0.42 ES:SE:LP:AF:SS:ID -0.07:0.04:1.3279:0.42:69360:rs11807848
1 1062638 rs9442373 C A . PASS AF=0.54 ES:SE:LP:AF:SS:ID 0.07:0.04:1.38722:0.54:69360:rs9442373
1 1064535 rs6682475 G C . PASS AF=0.72 ES:SE:LP:AF:SS:ID 0.08:0.05:1.13668:0.72:69360:rs6682475
1 1064979 rs2298217 C T . PASS AF=0.15 ES:SE:LP:AF:SS:ID -0.02:0.03:0.229148:0.15:69360:rs2298217
1 1077064 rs4970357 C A . PASS AF=0.91 ES:SE:LP:AF:SS:ID 0.01:0.04:0.0809219:0.91:69360:rs4970357
1 1087683 rs9442380 T C . PASS AF=0.92 ES:SE:LP:AF:SS:ID 0.02:0.04:0.161151:0.92:69360:rs9442380
1 1089262 rs4970358 A G . PASS AF=0.96 ES:SE:LP:AF:SS:ID 0.01:0.07:0.0861861:0.96:69360:rs4970358
1 1097335 rs9442385 T G . PASS AF=0.93 ES:SE:LP:AF:SS:ID 0.01:0.04:0.0555173:0.93:69360:rs9442385
1 1099342 rs9660710 A C . PASS AF=0.93 ES:SE:LP:AF:SS:ID 0:0.04:0.0315171:0.93:69360:rs9660710
1 1100217 rs1891905 C T . PASS AF=0.95 ES:SE:LP:AF:SS:ID 0.03:0.05:0.30103:0.95:69360:rs1891905
1 1120431 rs1320571 G A . PASS AF=0.04 ES:SE:LP:AF:SS:ID -0.01:0.07:0.0655015:0.04:69360:rs1320571
1 1121014 rs3813204 G A . PASS AF=0.12 ES:SE:LP:AF:SS:ID -0.04:0.06:0.244125:0.12:69360:rs3813204
1 1121794 rs11260549 G A . PASS AF=0.12 ES:SE:LP:AF:SS:ID 0:0.03:0.0555173:0.12:69360:rs11260549
1 1124663 rs6684820 G A . PASS AF=0.26 ES:SE:LP:AF:SS:ID -0.01:0.02:0.200659:0.26:69360:rs6684820
1 1125553 rs10907174 A T . PASS AF=0.21 ES:SE:LP:AF:SS:ID 0:0.03:0.0362122:0.21:69360:rs10907174
1 1129672 rs11260554 G T . PASS AF=0.12 ES:SE:LP:AF:SS:ID 0:0.03:0.0268721:0.12:69360:rs11260554
1 1130727 rs10907175 A C . PASS AF=0.09 ES:SE:LP:AF:SS:ID 0.02:0.04:0.167491:0.09:69360:rs10907175