Multitrait GWAS to Connect Disease Variants and Biological Mechanisms

Overview

Journal PLoS Genet

Specialty Genetics

Date 2021 Aug 30

PMID 34460823

Citations 16

Authors

Hanna Julienne

Vincent Laville

Zachary R McCaw

Zihuai He

Vincent Guillemot

Carla Lasry

Andrey Ziyatdinov

Cyril Nerin

Amaury Vaysse

Pierre Lechat

Herve Menager

Wilfried Le Goff

Marie-Pierre Dube

Peter Kraft

Iuliana Ionita-Laza

Bjarni J Vilhjalmsson

Hugues Aschard

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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Joint testing of rare variant burden scores using non-negative least squares.

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The goldmine of GWAS summary statistics: a systematic review of methods and tools.

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Meta-analysis of six dairy cattle breeds reveals biologically relevant candidate genes for mastitis resistance.

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Trait selection strategy in multi-trait GWAS: Boosting SNP discoverability.

Suzuki Y, Menager H, Brancotte B, Vernet R, Nerin C, Boetto C HGG Adv. 2024; 5(3):100319.

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