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bioRxiv · 10.1101/2022.04.13.488214

Fast Kernel-based Association Testing of non-linear genetic effects for Biobank-scale data

Fu, B.·Pazokitoroudi, A.·Sudarshan, M.·Subramanian, L.·Sankararaman, S.
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Abstract

Our knowledge of non-linear genetic effects on complex traits remains limited, in part, due to the modest power to detect such effects. While kernel-based tests offer a powerful approach to test for nonlinear relationships between sets of genetic variants and traits, current approaches cannot be applied to Biobank-scale datasets containing hundreds of thousands of individuals. We propose, FastKAST, a Kernel-based approach that can test for non-linear effects of a set of variants on a trait. FastKAST provides calibrated hypothesis tests while enabling analysis of Biobank-scale datasets with hundreds of thousands of individuals. We applied FastKAST to thirty quantitative traits measured across {approx} 300 K unrelated white British individuals in the UK Biobank to detect sets of variants with nonlinear effects at genome-wide significance.

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Fu, B., Pazokitoroudi, A., Sudarshan, M., Subramanian, L., Sankararaman, S.. 2022-04-14. Fast Kernel-based Association Testing of non-linear genetic effects for Biobank-scale data. https://doi.org/10.1101/2022.04.13.488214

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