PLoS Genetics (Aug 2021)

Multitrait GWAS to connect disease variants and biological mechanisms.

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

DOI
https://doi.org/10.1371/journal.pgen.1009713
Journal volume & issue
Vol. 17, no. 8
p. e1009713

Abstract

Read online

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 variants 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.