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bioRxiv · 10.1101/2021.10.15.464608

Kernel-based genetic association analysis for microbiome phenotypes identifies host genetic drivers of beta-diversity

Liu, H.·Ling, W.·Hua, X.·Moon, J.-Y.·Williams-Nguyen, J. S.·Zhan, X.·Plantinga, A. M.·Zhao, N.·Zhang, A.·Knight, R.·Qi, Q.·Burk, R. D.·Kaplan, R. C.·Wu, M. C.
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Abstract

Understanding human genetic influences on the gut microbiota helps elucidate the mechanisms by which genetics affects health outcomes. We propose a novel approach, the covariate-adjusted kernel RV (KRV) framework, to map genetic variants associated with microbiome beta-diversity, which focuses on overall shifts in the microbiota. The proposed KRV framework improves statistical power by capturing intrinsic structure within the genetic and microbiome data while reducing the multiple-testing burden. We apply the covariate-adjusted KRV test to the Hispanic Community Health Study/Study of Latinos in a genome-wide association analysis (first gene-level, then variant-level) for microbiome beta-diversity. We have identified an immunity-related gene, IL23R, reported in previous association studies and discovered 3 other novel genes, 2 of which are involved in immune functions or autoimmune disorders. Our findings highlight the value of the KRV as a powerful microbiome GWAS approach and support an important role of immunity-related genes in shaping the gut microbiome composition.

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Liu, H., Ling, W., Hua, X., Moon, J.-Y., Williams-Nguyen, J. S., Zhan, X., Plantinga, A. M., Zhao, N., Zhang, A., Knight, R., Qi, Q., Burk, R. D., Kaplan, R. C., Wu, M. C.. 2021-10-16. Kernel-based genetic association analysis for microbiome phenotypes identifies host genetic drivers of beta-diversity. https://doi.org/10.1101/2021.10.15.464608

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