Post by Jian Yang on Jun 10, 2015 7:14:44 GMT
LD score is defined as the sum of LD r2 between a variant and all the variants in a region.
Example - calculating LD score to stratify SNPs
--ld-wind 10000
The default value is L = 10000 (in Kb unit), i.e. L = 10Mb. The genome is chopped into segments with length of L for LD calculation. Two adjacent segments are overlapped. The size of the overlap is L/2.
--ld-rsq-cutoff 0
The default value is 0. LD r2 smaller than this value will be ignored in the calculated. If the threshold is > 0, the LD score estimate is biased since it's alway positive. The LD score generated from this option can be used for stratifying SNPs (see GREML-LDMS).
Output
mean_rsq: mean LD r2 between the target SNP and all other SNPs in the window.
snp_num: number of SNPs used in the calculation
max_rsq: maximum LD r2 between the target SNP and its best tagging SNP in the window.
ldscore: LD score
LD score is calculated as
Example - calculating LD score for LDSC regression
--ld-score-adj
LD r2 is alway positive which is not an unbiased estimate of squared correlation (rho2). The adjustment is r2adj = r2 - [(1 - r2) / (n -2)], where n is the sample size (Bulik-Sullivan et al. 2015 Nat Genet).
The output from this analysis can be used for LDSC regression analysis. We do not recommend using the --ld-rsq-cutoff option in this analysis. Otherwise, the LD score estimate is biased.
--ld-score-multi
Creating LD score of each SNP against multiple SNP set. This option can be used to perform multi-component LDSC regression analysis following Finucane et al. (2015 Nat Genet). Note that the --ld-score-adj option also applies to this analysis.
Output - the same as above.
Example - calculating LD scores for multi-component LDSC regression
Note that this is an analysis of calculating the LD score for each SNP against multiple SNP sets, e.g. the LD score of each SNP against all SNPs in exons and that against all SNPs in introns.
Input format
test_multi_snplist.txt
Output - an example of calculating LD score of SNP against two SNP sets
References
LD score regression analysis: Bulik-Sullivan BK, Loh PR, Finucane HK, Ripke S, Yang J, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Patterson N, Daly MJ, Price AL, Neale BM (2015) LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet, 47: 291-295.
GCTA software: Yang J, Lee SH, Goddard ME and Visscher PM. (2011) GCTA: a tool for Genome-wide Complex Trait Analysis. Am J Hum Genet, 88: 76-82. [PubMed ID: 21167468]
Example - calculating LD score to stratify SNPs
gcta64 --bfile test --ld-score --ld-wind 1000 --ld-rsq-cutoff 0.01 --out test--ld-wind 10000
The default value is L = 10000 (in Kb unit), i.e. L = 10Mb. The genome is chopped into segments with length of L for LD calculation. Two adjacent segments are overlapped. The size of the overlap is L/2.
--ld-rsq-cutoff 0
The default value is 0. LD r2 smaller than this value will be ignored in the calculated. If the threshold is > 0, the LD score estimate is biased since it's alway positive. The LD score generated from this option can be used for stratifying SNPs (see GREML-LDMS).
Output
SNP chr bp MAF mean_rsq snp_num max_rsq ldscore
rs12260013 10 66326 0.0709329 0.0475853 2211 0.807478 106.211
...
mean_rsq: mean LD r2 between the target SNP and all other SNPs in the window.
snp_num: number of SNPs used in the calculation
max_rsq: maximum LD r2 between the target SNP and its best tagging SNP in the window.
ldscore: LD score
LD score is calculated as
1 + mean_rsq * snp_numExample - calculating LD score for LDSC regression
gcta64 --bfile test --ld-score --ld-wind 1000 --ld-score-adj --out test--ld-score-adj
LD r2 is alway positive which is not an unbiased estimate of squared correlation (rho2). The adjustment is r2adj = r2 - [(1 - r2) / (n -2)], where n is the sample size (Bulik-Sullivan et al. 2015 Nat Genet).
The output from this analysis can be used for LDSC regression analysis. We do not recommend using the --ld-rsq-cutoff option in this analysis. Otherwise, the LD score estimate is biased.
--ld-score-multi
Creating LD score of each SNP against multiple SNP set. This option can be used to perform multi-component LDSC regression analysis following Finucane et al. (2015 Nat Genet). Note that the --ld-score-adj option also applies to this analysis.
Output - the same as above.
Example - calculating LD scores for multi-component LDSC regression
gcta64 --bfile test --ld-score-multi test_multi_snplist.txt --ld-wind 1000 --out test Note that this is an analysis of calculating the LD score for each SNP against multiple SNP sets, e.g. the LD score of each SNP against all SNPs in exons and that against all SNPs in introns.
Input format
test_multi_snplist.txt
test_snp_set1.snplist
test_snp_set2.snplist
...
Output - an example of calculating LD score of SNP against two SNP sets
SNP chr bp MAF mean_rsq_1 snp_num_1 max_rsq1 ldscore1 mean_rsq_2 snp_num_2 max_rsq2 ldscore2
rs4475691 1 836671 0.197698 0.000867814 499 0.216874 0.000308932 500 0.0022564
rs28705211 1 890368 0.278112 0.000911328 499 0.216874 0.000237098 500 0.00254858
rs9777703 1 918699 0.0301614 0.00240581 499 0.854464 0.000222185 500 0.00222427
...
References
LD score regression analysis: Bulik-Sullivan BK, Loh PR, Finucane HK, Ripke S, Yang J, Schizophrenia Working Group of the Psychiatric Genomics Consortium, Patterson N, Daly MJ, Price AL, Neale BM (2015) LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet, 47: 291-295.
GCTA software: Yang J, Lee SH, Goddard ME and Visscher PM. (2011) GCTA: a tool for Genome-wide Complex Trait Analysis. Am J Hum Genet, 88: 76-82. [PubMed ID: 21167468]