2023 Articles

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

Ma, Shiyang; Wang, Chen; Khan, Atlas; Liu, Linxi; Dalgleish, James; Kiryluk, Krzysztof; He, Zihuai; Ionita-Laza, Iuliana

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.