Journal Article

DKFZ-2025-03002

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Genetic architecture and mechanisms of host-microbiome interactions from a multi-cohort analysis of outbred laboratory rats.

Tonnelé, H. ; Chen, D. ; Morillo, F. ; Garcia-Calleja, J. ; Chitre, A. S. ; Johnson, B. B. ; Sanches, T. M. ; Cheng, R. ; Bonder, M. J. ; Gonzalez, A. ; Kosciolek, T. ; George, A. M. ; Han, W. ; Holl, K. ; Horvath, A. ; Ishiwari, K. ; King, C. P. ; Lamparelli, A. C. ; Martin, C. D. ; Martinez, A. G. ; Netzley, A. H. ; Tripi, J. A. ; Wang, T. ; Bosch, E. ; Doris, P. A. ; Stegle, O.DKFZ* ; Chen, H. ; Flagel, S. B. ; Meyer, P. J. ; Richards, J. B. ; Robinson, T. E. ; Solberg Woods, L. C. ; Polesskaya, O. ; Knight, R. ; Palmer, A. A. ; Baud, A.

2025
Springer Nature [London]

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'.

Keyword(s): Animals (MeSH) ; Rats (MeSH) ; Gastrointestinal Microbiome: genetics (MeSH) ; Sialyltransferases: genetics (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Cohort Studies (MeSH) ; Phenotype (MeSH) ; Multifactorial Inheritance (MeSH) ; Host Microbial Interactions: genetics (MeSH) ; Female (MeSH) ; Sialyltransferases

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Contributing Institute(s):

1. B260 Bioinformatik der Genomik und Systemgenetik (B260)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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