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.
Show 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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