Estimating cross-population genetic correlations of causal effect sizes

Genet Epidemiol. 2019 Mar;43(2):180-188. doi: 10.1002/gepi.22173. Epub 2018 Nov 25.


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 populations, which drive tagging effects. Here, we derive the value of the ratio ρ g / ρ b as a function of LD in each population. By applying existing methods to obtain estimates of ρ g , we can use this ratio to estimate ρ b . Our estimates of ρ 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.

Keywords: genetic architecture; genetic correlation; multiethnic.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aging / genetics
  • Arthritis, Rheumatoid / genetics
  • Biological Specimen Banks
  • Databases, Genetic
  • Diabetes Mellitus, Type 2 / genetics
  • Genetics, Population*
  • Genotype
  • Humans
  • Phenotype
  • Quantitative Trait, Heritable
  • United Kingdom