RT Journal Article
SR Electronic
T1 Kernel-based genetic association analysis for microbiome phenotypes identifies host genetic drivers of beta-diversity
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.10.15.464608
DO 10.1101/2021.10.15.464608
A1 Hongjiao Liu
A1 Wodan Ling
A1 Xing Hua
A1 Jee-Young Moon
A1 Jessica S. Williams-Nguyen
A1 Xiang Zhan
A1 Anna M. Plantinga
A1 Ni Zhao
A1 Angela Zhang
A1 Rob Knight
A1 Qibin Qi
A1 Robert D. Burk
A1 Robert C. Kaplan
A1 Michael C. Wu
YR 2021
UL http://biorxiv.org/content/early/2021/10/16/2021.10.15.464608.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.