Local genetic correlation gives insights into the shared genetic architecture of complex traits

Abstract

AbstractAlthough genetic correlations between complex traits provide valuable insights into epidemiological and etiological studies, a precise quantification of which genomic regions contribute to the genome-wide genetic correlation is currently lacking. Here, we introduce ρ-HESS, a technique to quantify the correlation between pairs of traits due to genetic variation at a small region in the genome. Our approach only requires GWAS summary data and makes no distributional assumption on the causal variant effects sizes while accounting for linkage disequilibrium (LD) and overlapping GWAS samples. We analyzed large-scale GWAS summary data across 35 complex traits, and identified 27 genomic regions that contribute significantly to the genetic correlation among these traits. Notably, we find 7 genomic regions that contribute to the genetic correlation of 12 pairs of traits that show negligible genome-wide correlation, further showcasing the power of local genetic correlation analyses. Finally, we leverage the distribution of local genetic correlations across the genome to assign putative direction of causality for 15 pairs of traits.