TY - JOUR T1 - Localizing components of shared transethnic genetic architecture of complex traits from GWAS summary data JF - bioRxiv DO - 10.1101/858431 SP - 858431 AU - Huwenbo Shi AU - Kathryn S. Burch AU - Ruth Johnson AU - Malika K. Freund AU - Gleb Kichaev AU - Nicholas Mancuso AU - Astrid M. Manuel AU - Natalie Dong AU - Bogdan Pasaniuc Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/12/12/858431.abstract N2 - Despite strong transethnic genetic correlations reported in the literature for many complex traits, the non-transferability of polygenic risk scores across populations implies 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. ER -