Multitrait GWAS to connect disease variants and biological mechanisms

by Hanna Julienne, Vincent Laville, Zachary R. McCaw, Zihuai He, Vincent Guillemot, Carla Lasry, Andrey Ziyatdinov, Cyril Nerin, Amaury Vaysse, Pierre Lechat, Herv é Ménager, Wilfried Le Goff, Marie-Pierre Dube, Peter Kraft, Iuliana Ionita-Laza, Bjarni J. Vilhjálmsson, Hugues Aschard

Genome-wide association studies (GWASs) have uncovered a wealth of associations between common variants and human phenotypes. Here, we present an integrative analysis of GWAS summary statistics from 36 phenotypes to decipher multitrait genetic architecture and its link with biological mechanisms. Our framework incorporates multitrait association mapping along with an investigation of the breakdown of genetic associations into clusters of variants harboring similar multitrait association profiles. Focusing on two subsets of immunity and metabolism phenotypes, we then demonstrate how genetic v ariants within clusters can be mapped to biological pathways and disease mechanisms. Finally, for the metabolism set, we investigate the link between gene cluster assignment and the success of drug targets in randomized controlled trials.

Source: PLoS Genetics - August 30, 2021 Category: Genetics & Stem Cells Authors: Hanna Julienne Source Type: research