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• W2990224897 abstract "Abstract Despite strong transethnic genetic correlations reported in the literature for many complex traits, the non-transferability of polygenic risk scores across populations suggests the presence of population-specific components of genetic architecture. We propose an approach that models GWAS summary data for one trait in two populations to estimate genome-wide proportions of population-specific/shared causal SNPs. In simulations across various genetic architectures, we show that our approach yields approximately unbiased estimates with in-sample LD and slight upward-bias with out-of-sample LD. We analyze 9 complex traits in individuals of East Asian and European ancestry, restricting to common SNPs (MAF > 5%), and find that most common causal SNPs are shared by both populations. Using the genome-wide estimates as priors in an empirical Bayes framework, we perform fine-mapping and observe that high-posterior SNPs (for both the population-specific and shared causal configurations) have highly correlated effects in East Asians and Europeans. In population-specific GWAS risk regions, we observe a 2.8x enrichment of shared high-posterior SNPs, suggesting that population-specific GWAS risk regions harbor shared causal SNPs that are undetected in the other GWAS due to differences in LD, allele frequencies, and/or sample size. Finally, we report enrichments of shared high-posterior SNPs in 53 tissue-specific functional categories and find evidence that SNP-heritability enrichments are driven largely by many low-effect common SNPs." @default.
• W2990224897 created "2019-12-05" @default.
• W2990224897 creator A5013091003 @default.
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• W2990224897 date "2019-11-29" @default.
• W2990224897 modified "2023-10-12" @default.
• W2990224897 title "Localizing components of shared transethnic genetic architecture of complex traits from GWAS summary data" @default.
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• W2990224897 doi "https://doi.org/10.1101/858431" @default.
• W2990224897 hasPublicationYear "2019" @default.
• W2990224897 type Work @default.
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