Genetic determinants of plasma protein levels in the Estonian population

Abstract

AbstractThe proteome holds great potential as an intermediate layer between the genome and phenome. Previous protein quantitative trait locus studies have focused mainly on describing the effects of common genetic variations on the proteome. Here, we assessed the impact of the common and rare genetic variations as well as the copy number variants (CNVs) on 326 plasma proteins measured in up to 500 individuals. We identified 184cisand 94transsignals for 157 protein traits, which were further fine-mapped to credible sets for 101cisand 87transsignals for 151 proteins. Rare genetic variation contributed to the levels of 7 proteins, with 5cisand 14transassociations. CNVs were associated with the levels of 11 proteins (7cisand 5trans), examples including a 3q12.1 deletion acting as a hub for multipletransassociations; and a CNV overlappingNAIP, a sensor component of the NAIP-NLRC4 inflammasome which is affecting pro-inflammatory cytokine interleukin 18 levels. In summary, this work presents a comprehensive resource of genetic variation affecting the plasma protein levels and provides the interpretation of identified effects.