Genetic determinants of plasma protein levels in the Estonian population

• Published in: Scientific reports Vol. 14; no. 1; p. 7694
• Main Authors: Kalnapenkis, Anette, Jõeloo, Maarja, Lepik, Kaido, Kukuškina, Viktorija, Kals, Mart, Alasoo, Kaur, Mägi, Reedik, Esko, Tõnu, Võsa, Urmo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 02.04.2024; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/191; 631/208/212; 631/208/480; Blood Proteins - genetics; Copy number; DNA Copy Number Variations - genetics; DNA sequences; Estonia; Gene mapping; Genetic diversity; Genetic variation; Genome-Wide Association Study; Genomes; Humanities and Social Sciences; Humans; Inflammasomes; Inflammation; Interleukin 18; multidisciplinary; Plasma proteins; Polymorphism, Single Nucleotide; Proteins; Proteome - genetics; Proteomes; Quantitative trait loci; Quantitative Trait Loci - genetics; Science; Science (multidisciplinary); Estonia
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-57966-3

The 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 184 cis and 94 trans signals for 157 protein traits, which were further fine-mapped to credible sets for 101 cis and 87 trans signals for 151 proteins. Rare genetic variation contributed to the levels of 7 proteins, with 5 cis and 14 trans associations. CNVs were associated with the levels of 11 proteins (7 cis and 5 trans ), examples including a 3q12.1 deletion acting as a hub for multiple trans associations; and a CNV overlapping NAIP , 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.