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Genetics of human gut microbiome composition

By Alexander Kurilshikov, Carolina Medina-Gomez, Rodrigo Bacigalupe, Djawad Radjabzadeh, Jun Wang, Ayse Demirkan, Caroline I Le Roy, Juan Antonio Raygoza Garay, Casey T. Finnicum, Xingrong Liu, Daria V. Zhernakova, MJ Bonder, Tue H. Hansen, Fabian Frost, Malte Christoph Rühlemann, Williams Turpin, Jee-Young Moon, Han-Na Kim, Kreete Lüll, Elad Barkan, Shiraz A. Shah, Myriam Fornage, Joanna Szopinska-Tokov, Zachary D. Wallen, Dmitrii Borisevich, Lars Agreus, Anna Andreasson, Corinna Bang, Larbi Bedrani, Jordana T. Bell, Hans Bisgaard, Michael Boehnke, Dorret I. Boomsma, Robert D Burk, Annique Claringbould, Kenneth Croitoru, Gareth E. Davies, Cornelia M. van Duijn, Liesbeth Duijts, Gwen Falony, Jingyuan Fu, Adriaan van der Graaf, Torben Hansen, Georg Homuth, David A Hughes, Richard G Ijzerman, Matthew A Jackson, Vincent W.V. Jaddoe, Marie Joossens, Torben Jørgensen, Daniel Keszthelyi, Rob Knight, Markku Laakso, Matthias Laudes, Lenore J Launer, Wolfgang Lieb, Aldons J. Lusis, Ad A.M. Masclee, Henriette A. Moll, Zlatan Mujagic, Qi Qibin, Daphna Rothschild, Hocheol Shin, Søren J. Sørensen, Claire Steves, Jonathan Thorsen, Nicholas J. Timpson, Raul Y Tito, Sara Vieira-Silva, Uwe Volker, Henry Völzke, Urmo Võsa, KH Wade, Susanna Walter, Kyoko Watanabe, Stefan Weiss, Frank U Weiss, Omer Weissbrod, Harm-Jan Westra, Gonneke Willemsen, Haydeh Payami, Daisy M.A.E. Jonkers, Alejandro Arias Vasquez, Eco JC de Geus, Katie A. Meyer, Jakob Stokholm, Eran Segal, Elin Org, Cisca Wijmenga, Hyung-Lae Kim, Robert C. Kaplan, Tim D Spector, Andre G Uitterlinden, Fernando Rivadeneira, Andre Franke, Markus M. Lerch, L.H. Franke, Serena Sanna, M D’Amato, Oluf Pedersen, Andrew D. Paterson, Robert Kraaij, Jeroen Raes, Alexandra Zhernakova

Posted 28 Jun 2020
bioRxiv DOI: 10.1101/2020.06.26.173724

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed whole-genome genotypes and 16S fecal microbiome data from 18,473 individuals (25 cohorts). Microbial composition showed high variability across cohorts: we detected only 9 out of 410 genera in more than 95% of the samples. A genome-wide association study (GWAS) of host genetic variation in relation to microbial taxa identified 30 loci affecting microbome taxa at a genome-wide significant (P<5×10-8) threshold. Just one locus, the lactase ( LCT ) gene region, reached study-wide significance (GWAS signal P=8.6×10−21); it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.94×10−10<P<5×10−8) but enriched for taxa showing high heritability and for genes expressed in the intestine and brain. A phenome-wide association study and Mendelian randomization analyses identified enrichment of microbiome trait loci SNPs in the metabolic, nutrition and environment domains and indicated food preferences and diseases as mediators of genetic effects. ### Competing Interest Statement The authors have declared no competing interest.

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