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
Year of publication:
Journal title abbreviated:
Gut Microbes
Journal title long:
Gut microbes
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.