TY - JOUR
T1 - Genetic architecture and mechanisms of host-microbiome interactions from a multi-cohort analysis of outbred laboratory rats
AU - Tonnelé, Hélène
AU - Chen, Denghui
AU - Morillo, Felipe
AU - Garcia-Calleja, Jorge
AU - Chitre, Apurva S.
AU - Johnson, Benjamin B.
AU - Sanches, Thiago Missfeldt
AU - Cheng, Riyan
AU - Bonder, Marc Jan
AU - Gonzalez, Antonio
AU - Kosciolek, Tomasz
AU - George, Anthony M.
AU - Han, Wenyan
AU - Holl, Katie
AU - Horvath, Aidan
AU - Ishiwari, Keita
AU - King, Christopher P.
AU - Lamparelli, Alexander C.
AU - Martin, Connor D.
AU - Martinez, Angel Garcia
AU - Netzley, Alesa H.
AU - Tripi, Jordan A.
AU - Wang, Tengfei
AU - Bosch, Elena
AU - Doris, Peter A.
AU - Stegle, Oliver
AU - Chen, Hao
AU - Flagel, Shelly B.
AU - Meyer, Paul J.
AU - Richards, Jerry B.
AU - Robinson, Terry E.
AU - Solberg Woods, Leah C.
AU - Polesskaya, Oksana
AU - Knight, Rob
AU - Palmer, Abraham A.
AU - Baud, Amelie
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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”.
AB - 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”.
UR - https://www.scopus.com/pages/publications/105025172099
U2 - 10.1038/s41467-025-66105-z
DO - 10.1038/s41467-025-66105-z
M3 - Article
C2 - 41413022
AN - SCOPUS:105025172099
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 10126
ER -