Application of the distance-based F test in an mGWAS investigating β diversity of intestinal microbiota identifies variants in SLC9A8 (NHE8) and 3 other loci.

Malte C Rühlemann, Frauke Degenhardt, Louise B Thingholm, Jun Wang, Jurgita Skiecevičienė, Philipp Rausch, Johannes R Hov, Wolfgang Lieb, Tom H Karlsen, Matthias Laudes, John F Baines, Femke-Anouska Heinsen, Andre Franke

Journal: Gut microbes 2018;9(1):68-75

PMID: 28816579

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Abstract

Factors shaping the human intestinal microbiota range from environmental influences, like smoking and exercise, over dietary patterns and disease to the host's genetic variation. Recently, we could show in a microbiome genome-wide association study (mGWAS) targeting genetic variation influencing the β diversity of gut microbial communities, that approximately 10% of the overall gut microbiome variation can be explained by host genetics. Here, we report on the application of a new method for genotype-β-diversity association testing, the distance-based F (DBF) test. With this we identified 4 loci with genome-wide significant associations, harboring the genes CBEP4, SLC9A8, TNFSF4, and SP140, respectively. Our findings highlight the utility of the high-performance DBF test in β diversity GWAS and emphasize the important role of host genetics and immunity in shaping the human intestinal microbiota.

Address: a Institute of Clinical Molecular Biology , Christian-Albrechts-University of Kiel , Kiel , Germany.; b Evolutionary Genomics , Max Planck Institute for Evolutionary Biology , Plön , Germany.; c Institute for Experimental Medicine , Christian-Albrechts-University of Kiel , Kiel , Germany.; d Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation , University Hospital Rikshospitalet , Oslo , Norway.; e K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine , University of Oslo , Oslo , Norway.; f Research Institute of Internal Medicine , Oslo University Hospital Rikshospitalet , Oslo , Norway.; g Section of Gastroenterology, Department of Transplantation Medicine , Oslo University Hospital Rikshospitalet , Oslo , Norway.; h Institute of Epidemiology , Christian-Albrechts-University of Kiel , Kiel , Germany.; i Department of Clinical Medicine , University of Bergen , Bergen , Norway.; j Department of Internal Medicine I , University Hospital S.-H. (UKSH, Campus Kiel) , Kiel , Germany.

DOI: 10.1080/19490976.2017.1356979

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MeSH Terms: Antigens, Nuclear, Bacteria, Biodiversity, Gastrointestinal Microbiome, Genetic Loci, Genetic Variation, Genome-Wide Association Study, Host-Pathogen Interactions, Humans, Immunity, Models, Statistical, OX40 Ligand, RNA-Binding Proteins, Reproducibility of Results, Sodium-Hydrogen Exchangers, Transcription Factors