Application of the distance-based F test in an mGWAS investigating beta diversity of intestinal microbiota identifies variants in SLC9A8 (NHE8) and three 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
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Journal title abbreviated:
Gut Microbes
Journal title long:
Gut microbes
Impact factor:
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 beta 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-beta-diversity association testing, the distance-based F (DBF) test. With this we identified four 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 beta diversity GWAS and emphasize the important role of host genetics and immunity in shaping the human intestinal microbiota.