An integrative analysis of genomic and exposomic data for complex traits and phenotypic prediction.

Scientific Reports
Xuan Zhou, S Hong Lee

Abstract

Complementary to the genome, the concept of exposome has been proposed to capture the totality of human environmental exposures. While there has been some recent progress on the construction of the exposome, few tools exist that can integrate the genome and exposome for complex trait analyses. Here we propose a linear mixed model approach to bridge this gap, which jointly models the random effects of the two omics layers on phenotypes of complex traits. We illustrate our approach using traits from the UK Biobank (e.g., BMI and height for N ~ 35,000) with a small fraction of the exposome that comprises 28 lifestyle factors. The joint model of the genome and exposome explains substantially more phenotypic variance and significantly improves phenotypic prediction accuracy, compared to the model based on the genome alone. The additional phenotypic variance captured by the exposome includes its additive effects as well as non-additive effects such as genome-exposome (gxe) and exposome-exposome (exe) interactions. For example, 19% of variation in BMI is explained by additive effects of the genome, while additional 7.2% by additive effects of the exposome, 1.9% by exe interactions and 4.5% by gxe interactions. Correspondingly, the pre...Continue Reading

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Citations

Dec 18, 2021·Frontiers in Genetics·Bart FerwerdaKoos Zwinderman

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