Abstract
Fully characterizing the genetic architecture of circulating proteins in multi-ancestry populations provides an unprecedented opportunity to gain insights into the etiology of complex diseases. We characterized and contrasted the genetic associations of plasma proteomes in 9,455 participants of European and African (19.8%) ancestry from the Atherosclerosis Risk in Communities Study. Of 4,651 proteins, 1,408 and 2,565 proteins had protein-quantitative trait loci (pQTLs) identified in African and European ancestry respectively, and twelve unreported potentially causal protein-disease relationships were identified. Shared pQTLs across the two ancestries were detected in 1,113 aptamer-region pairs pQTLs, where 53 of them were not previously reported (all trans pQTLs). Sixteen unique protein-cardiovascular trait pairs were colocalized in both European and African ancestry with the same candidate causal variants. Our systematic cross-ancestry comparison provided a reliable set of pQTLs, highlighted the shared and distinct genetic architecture of proteome in two ancestries, and demonstrated possible biological mechanisms underlying complex diseases.