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Genetics of human gut microbiome composition [article]

Alexander Kurilshikov, Carolina Medina-Gomez, Rodrigo Bacigalupe, Djawad Radjabzadeh, Jun Wang, Ayse Demirkan, Caroline I Le Roy, Juan Antonio Raygoza Garay, Casey Finnicum, Xingrong Liu, Daria Zhernakova, Marc Jan Bonder (+92 others)
2020 bioRxiv   pre-print

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https://web.archive.org/web/20201107113936/https://www.biorxiv.org/content/biorxiv/early/2020/07/12/2020.06.26.173724.full.pdf

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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
more » ... ant (P<5x10-8) threshold. Just one locus, the lactase (LCT) gene region, reached study-wide significance (GWAS signal P=8.6x10-21); it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.94x10-10<P<5x10-8) 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 mbQTL SNPs in the metabolic, nutrition and environment domains and indicated food preferences and diseases as mediators of genetic effects.
doi:10.1101/2020.06.26.173724 fatcat:5ek7n4ly6fbivf6s7ksg2jrspy
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Alexander Kurilshikov, Carolina Medina-Gomez, Rodrigo Bacigalupe, Djawad Radjabzadeh, Jun Wang, Ayse Demirkan, Caroline I Le Roy, Juan Antonio Raygoza Garay, Casey Finnicum, Xingrong Liu, Daria Zhernakova, Marc Jan Bonder, Tue H Hansen, Fabian Frost, Malte C Ruhlemann, Williams Turpin, Jee-Young Moon, Han-Na Kim, Kreete Lull, Elad Barkan, Shiraz A Shah, Myriam Fornage, Joanna Szopinska-Tokov, Zachary Wallen, Dmitrii Borisevich, Lars Agreus, Anna Andreasson, Corinna Bang, Larbi Bedrani, Jordana Tzenova Bell, Hans Bisgaard, Michael Boehnke, Dorret I Boomsma, Robert D Burk, Annique Claringbould, Kenneth Croitoru, Gareth Davies, Cornelia 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 Joergensen, Daniel Keszthelyi, Rob Knight, Markku Laakso, Matthias Laudes, Lenore J Launer, Wolfgang Lieb, Aldons Jake Lusis, Ad A.M. Masclee, Henriette A. Moll, Zlatan Mujagic, Qi Qibin, Daphna Rothschild, Hocheol Shin, Soren Sorensen, Claire Steves, Jonathan Thorsen, Nicholas J Timpson, Raul Y Tito, Sara Vieira-Silva, Uve Voelker, Henry J Voelzke, Urmo Vosa, Kaitlin H 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 J.C. de Geus, Katie A. Meyer, Jakob Stokholm, Eran Segal, Elin Org, Cisca Wijmenga, Hyung-Lae Kim, Robert Kaplan, Timothy Spector, Andre G Uitterlinden, Fernando Rivadeneira, Andre Franke, Markus M Lerch, Lude Franke, Serena Sanna, Mauro D'Amato, Oluf Pedersen, Andrew D Paterson, Robert Kraaij, Jeroen Raes, Alexandra Zhernakova. "Genetics of human gut microbiome composition." bioRxiv (2020)