Genetic architecture and mechanisms of host-microbiome interactions from a multi-cohort analysis of outbred laboratory rats
Abstract
Abstract The intestinal microbiome influences health and disease. Its composition is affected by host genetics and environmental exposures. Understanding host genetic effects is critical but challenging in humans, due to the difficulty of detecting, mapping and interpreting them. To address this, we analyse host genetic effects in four cohorts of outbred laboratory rats exposed to distinct but controlled environments. We show that polygenic host genetic effects are consistent across cohort environments. We identify three replicated microbiome-associated loci, one of which involves the sialyltransferase gene St6galnac1 and Paraprevotella . We find a similar association in a human cohort, between ST6GAL1 and Paraprevotella , both of which have been linked with immune and infectious diseases. Moreover, we find indirect (i.e. social) genetic effects on microbiome phenotypes, which substantially increase the total genetic variance. Finally, we identify a novel mechanism whereby indirect genetic effects can contribute to “missing heritability”.
Article Details
Authors (36)
Hélène Tonnelé
Denghui Chen
Felipe Morillo
Jorge Garcia-Calleja
Institute of Evolutionary Biology (Consejo Superior de Investigaciones Científicas - Universitat Pompeu Fabra), Department of Medicine and Life Sciences, Universitat Pompeu Fabra
Apurva S. Chitre
Benjamin B. Johnson
Thiago Missfeldt Sanches
Riyan Cheng
Marc Jan Bonder
Antonio Gonzalez
Tomasz Kosciolek
Anthony M. George
Wenyan Han
Katie Holl
Aidan Horvath
Keita Ishiwari
Christopher P. King
Alexander C. Lamparelli
Connor D. Martin
Angel Garcia Martinez
Alesa H. Netzley
Jordan A. Tripi
Tengfei Wang
Elena Bosch
Institute of Evolutionary Biology (Consejo Superior de Investigaciones Científicas - Universitat Pompeu Fabra), Department of Medicine and Life Sciences, Universitat Pompeu Fabra
Peter A. Doris
Oliver Stegle
Hao Chen
Shelly B. Flagel
Paul J. Meyer
Jerry B. Richards
Terry E. Robinson
Leah C. Solberg Woods
Oksana Polesskaya
Rob Knight
Department of Pediatrics
Abraham A. Palmer
Amelie Baud