BIGKnock: fine-mapping gene-based associations via knockoff analysis of biobank-scale data

Autor: Shiyang Ma, Chen Wang, Atlas Khan, Linxi Liu, James Dalgleish, Krzysztof Kiryluk, Zihuai He, Iuliana Ionita-Laza
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Genome Biology, Vol 24, Iss 1, Pp 1-28 (2023)
Druh dokumentu: article
ISSN: 1474-760X
DOI: 10.1186/s13059-023-02864-6
Popis: Abstract We propose BIGKnock (BIobank-scale Gene-based association test via Knockoffs), a computationally efficient gene-based testing approach for biobank-scale data, that leverages long-range chromatin interaction data, and performs conditional genome-wide testing via knockoffs. BIGKnock can prioritize causal genes over proxy associations at a locus. We apply BIGKnock to the UK Biobank data with 405,296 participants for multiple binary and quantitative traits, and show that relative to conventional gene-based tests, BIGKnock produces smaller sets of significant genes that contain the causal gene(s) with high probability. We further illustrate its ability to pinpoint potential causal genes at $$\sim 80\%$$ ∼ 80 % of the associated loci.
Databáze: Directory of Open Access Journals