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A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits.

Accepted version
Peer-reviewed

Type

Article

Change log

Authors

Foley, Christopher N  ORCID logo  https://orcid.org/0000-0002-0970-2610
Staley, James R 
Breen, Philip G 
Sun, Benjamin B 

Abstract

Genome-wide association studies (GWAS) have identified thousands of genomic regions affecting complex diseases. The next challenge is to elucidate the causal genes and mechanisms involved. One approach is to use statistical colocalization to assess shared genetic aetiology across multiple related traits (e.g. molecular traits, metabolic pathways and complex diseases) to identify causal pathways, prioritize causal variants and evaluate pleiotropy. We propose HyPrColoc (Hypothesis Prioritisation for multi-trait Colocalization), an efficient deterministic Bayesian algorithm using GWAS summary statistics that can detect colocalization across vast numbers of traits simultaneously (e.g. 100 traits can be jointly analysed in around 1 s). We perform a genome-wide multi-trait colocalization analysis of coronary heart disease (CHD) and fourteen related traits, identifying 43 regions in which CHD colocalized with ≥1 trait, including 5 previously unknown CHD loci. Across the 43 loci, we further integrate gene and protein expression quantitative trait loci to identify candidate causal genes.

Description

Keywords

Algorithms, Computational Biology, Coronary Disease, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomics, Humans, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Reproducibility of Results, Risk Factors

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

12

Publisher

Springer Science and Business Media LLC

Rights

All rights reserved
Sponsorship
British Heart Foundation (None)
NHS Blood and Transplant (NHSBT) (WP12-01)
Wellcome Trust (204623/Z/16/Z)
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC)
Medical Research Council (MR/L003120/1)
Medical Research Council (MC_UU_00002/7)
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