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Estimating cross-population genetic correlations of causal effect sizes.

ABSTRACT: Recent studies have examined the genetic correlations of single-nucleotide polymorphism (SNP) effect sizes across pairs of populations to better understand the genetic architectures of complex traits. These studies have estimated ? g , the cross-population correlation of joint-fit effect sizes at genotyped SNPs. However, the value of ? g depends both on the cross-population correlation of true causal effect sizes ( ? b ) and on the similarity in linkage disequilibrium (LD) patterns in the two populations, which drive tagging effects. Here, we derive the value of the ratio ? g / ? b as a function of LD in each population. By applying existing methods to obtain estimates of ? g , we can use this ratio to estimate ? b . Our estimates of ? b were equal to 0.55 ( SE?=?0.14) between Europeans and East Asians averaged across nine traits in the Genetic Epidemiology Research on Adult Health and Aging data set, 0.54 ( SE?=?0.18) between Europeans and South Asians averaged across 13 traits in the UK Biobank data set, and 0.48 ( SE?=?0.06) and 0.65 ( SE?=?0.09) between Europeans and East Asians in summary statistic data sets for type 2 diabetes and rheumatoid arthritis, respectively. These results implicate substantially different causal genetic architectures across continental populations.

SUBMITTER: Galinsky KJ

PROVIDER: S-EPMC6375794 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Estimating cross-population genetic correlations of causal effect sizes.

Galinsky Kevin J KJ Reshef Yakir A YA Finucane Hilary K HK Loh Po-Ru PR Zaitlen Noah N Patterson Nick J NJ Brown Brielin C BC Price Alkes L AL

Genetic epidemiology 20181125 2

Recent studies have examined the genetic correlations of single-nucleotide polymorphism (SNP) effect sizes across pairs of populations to better understand the genetic architectures of complex traits. These studies have estimated ρ g , the cross-population correlation of joint-fit effect sizes at genotyped SNPs. However, the value of ρ g depends both on the cross-population correlation of true causal effect sizes ( ρ b ) and on the similarity in linkage disequilibrium (LD) patterns in the two ...[more]

PMID: 30474154

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Estimating cross-population genetic correlations of causal effect sizes.

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Estimating cross-population genetic correlations of causal effect sizes.

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