Fast Kernel-based Association Testing of Non-linear Genetic Effects for Biobank-scale Data

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Aug 15

PMID 37582955

Authors

Boyang Fu

Ali Pazokitoroudi

Mukund Sudarshan

Zhengtong Liu

Lakshminarayanan Subramanian

Sriram Sankararaman

Affiliations

Soon will be listed here.

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 versatile approach to test for non-linear 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 quantitative trait. FastKAST provides calibrated hypothesis tests while enabling analysis of Biobank-scale datasets with hundreds of thousands of unrelated individuals from a homogeneous population. We apply FastKAST to 53 quantitative traits measured across ≈ 300 K unrelated white British individuals in the UK Biobank to detect sets of variants with non-linear effects at genome-wide significance.

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