Large-scale association analyses identify host factors influencing human gut microbiome composition

作者：Alexander Kurilshikov, Carolina Medina‐Gómez, Rodrigo Bacigalupe, Djawad Radjabzadeh, Jun Wang, Ayşe Demirkan, Caroline Ivanne Le Roy, Juan A. Raygoza Garay, Casey T. Finnicum, Xingrong Liu, Daria V. Zhernakova, Marc Jan Bonder, Tue H. Hansen, Fabian Frost, Malte Christoph Rühlemann, Williams Turpin, Jee‐Young Moon, Han‐Na Kim, Kreete Lüll, Elad Barkan, Shiraz Ali Shah, Myriam Fornage, Joanna Szopinska-Tokov, Zachary D. Wallen, Dmitrii Borisevich, Lars Agréus, Anna Andréasson, Corinna Bang, Larbi Bedrani, Jordana T. Bell, Hans Bisgaard, Michael Boehnke, Dorret Irene Boomsma, Robert David Burk, Annique Claringbould, Kenneth Croitoru, Gareth E. Davies, Cornelia M. van Duijn, Liesbeth Duijts, Gwen Falony, Jingyuan Fu, Adriaan van der Graaf, Torben F. Hansen, Georg Homuth, David Allan Hughes, Richard G. IJzerman, Matthew A Jackson, Vincent W. V. Jaddoe, Marie Joossens, Torben Jørgensen, Dániel Keszthelyi, Rob Knight, Markku Laakso, Matthias Laudes, Lenore J. Launer, Wolfgang Lieb, Aldons Jake Lusis, Ad Masclee, Henriëtte A. Moll, Zlatan Mujagic, Qibin Qi, Daphna Rothschild, Hocheol Shin, Søren Johannes Sørensen, Claire J. Steves, Jonathan Thorsen, Nicholas John Timpson, Raul Yhossef Tito, Sara Vieira‐Silva, Uwe Völker, Henry Völzke, Urmo Võsa, Kaitlin Hazel Wade, Susanna Walter, Kyoko Watanabe, Stefan Weiß, Frank Ulrich Weiß, Omer Weissbrod, Harm-Jan Westra, Gonneke A. H. M. Willemsen, Haydeh Payami, Daisy M.A.E. Jonkers, Alejandro Arias Vásquez, Eco J. C. de Geus, Katie A. Meyer, Jakob Stokholm, Eran Segal, Elin Org, Cisca Wijmenga, Hyung‐Lae Kim, Robert C. Kaplan, Tim D. Spector, André Gerardus Uitterlinden, Fernando Rivadeneira, André Franke, Markus M. Lerch, Lude Franke, Serena Sanna, Mauro D’Amato, Oluf Borbye Pedersen, Andrew D. Paterson, Robert Kraaij, Jeroen Raes, Alexandra Zhernakova · 发表于：Nature Genetics · 年份：2021 · DOI：10.1038/s41588-020-00763-1 · 被引用次数：1902 · 研究领域：Gut microbiota and health、Nutritional Studies and Diet、Food Security and Health in Diverse Populations

To study the effect of host genetics on gut microbiome composition, the MiBioGen consortium curated and analyzed genome-wide genotypes and 16S fecal microbiome data from 18,340 individuals (24 cohorts). Microbial composition showed high variability across cohorts: only 9 of 410 genera were detected in more than 95% of samples. A genome-wide association study of host genetic variation regarding microbial taxa identified 31 loci affecting the microbiome at a genome-wide significant (P < 5 × 10−8) threshold. One locus, the lactase (LCT) gene locus, reached study-wide significance (genome-wide association study signal: P = 1.28 × 10−20), and it showed an age-dependent association with Bifidobacterium abundance. Other associations were suggestive (1.95 × 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 identified enrichment of microbiome trait loci in the metabolic, nutrition and environment domains and suggested the microbiome might have causal effects in ulcerative colitis and rheumatoid arthritis. Analysis of human genotypes and 16S microbiome data of 18,473 individuals from 25 cohorts through a genome-wide association study, a phenome-wide association study and Mendelian randomization identifies host genetic and microbial trait associations.