A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits
Authors
Staley, James R.
Breen, Philip G.
Sun, Benjamin B.
Publication Date
2021-02-03Journal Title
Nature Communications
Publisher
Nature Publishing Group UK
Volume
12
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Foley, C. N., Staley, J. R., Breen, P. G., Sun, B. B., Kirk, P. D. W., Burgess, S., & Howson, J. M. M. (2021). A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits. Nature Communications, 12 (1) https://doi.org/10.1038/s41467-020-20885-8
Abstract
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.
Keywords
Article, /631/114/794, /631/208/191, /631/208/205/2138, /692/4019/592/2727, /38, /45, /45/43, /82/80, /119, /139, /45/41, /129, /141, article
Sponsorship
British Heart Foundation (BHF) (RG/13/13/30194)
RCUK | Medical Research Council (MRC) (MC UU 00002/7)
Identifiers
s41467-020-20885-8, 20885
External DOI: https://doi.org/10.1038/s41467-020-20885-8
This record's URL: https://www.repository.cam.ac.uk/handle/1810/317091
Rights
Attribution 4.0 International (CC BY 4.0)
Licence URL: https://creativecommons.org/licenses/by/4.0/
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