Estimating cross-population genetic correlations of causal effect sizes.

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 ρg , the cross-population correlation of joint-fit effect sizes at genotyped SNPs. However, the value of ρg depends both on the cross-population correlation of true causal effect sizes ( ρb ) 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 ρg/ρb as a function of LD in each population. By applying existing methods to obtain estimates of ρg , we can use this ratio to estimate ρb . Our estimates of ρb 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.