| Literature DB >> 33462485 |
Alexander Kurilshikov1, Carolina Medina-Gomez2,3, Rodrigo Bacigalupe4,5, Djawad Radjabzadeh2, Jun Wang4,5,6, Ayse Demirkan7,8, Caroline I Le Roy9, Juan Antonio Raygoza Garay10,11, Casey T Finnicum12, Xingrong Liu13, Daria V Zhernakova7,14, Marc Jan Bonder7, Tue H Hansen15, Fabian Frost16, Malte C Rühlemann17, Williams Turpin10,11, Jee-Young Moon18, Han-Na Kim19,20, Kreete Lüll21, Elad Barkan22, Shiraz A Shah23, Myriam Fornage24,25, Joanna Szopinska-Tokov26, Zachary D Wallen27, Dmitrii Borisevich15, Lars Agreus28, Anna Andreasson29, Corinna Bang17, Larbi Bedrani10, Jordana T Bell9, Hans Bisgaard23, Michael Boehnke30, Dorret I Boomsma31, Robert D Burk32,33, Annique Claringbould7, Kenneth Croitoru10,11, Gareth E Davies12,31, Cornelia M van Duijn34,35, Liesbeth Duijts3,36, Gwen Falony4,5, Jingyuan Fu7,37, Adriaan van der Graaf7, Torben Hansen15, Georg Homuth38, David A Hughes39,40, Richard G Ijzerman41, Matthew A Jackson9,42, Vincent W V Jaddoe3,34, Marie Joossens4,5, Torben Jørgensen43, Daniel Keszthelyi44,45, Rob Knight46,47,48, Markku Laakso49, Matthias Laudes50, Lenore J Launer51, Wolfgang Lieb52, Aldons J Lusis53,54, Ad A M Masclee44,45, Henriette A Moll36, Zlatan Mujagic44,45, Qi Qibin18, Daphna Rothschild22, Hocheol Shin55,56, Søren J Sørensen57, Claire J Steves9, Jonathan Thorsen23, Nicholas J Timpson39,40, Raul Y Tito4,5, Sara Vieira-Silva4,5, Uwe Völker38, Henry Völzke58, Urmo Võsa7, Kaitlin H Wade39,40, Susanna Walter59,60, Kyoko Watanabe61, Stefan Weiss16,38, Frank U Weiss16, Omer Weissbrod62, Harm-Jan Westra7, Gonneke Willemsen31, Haydeh Payami27, Daisy M A E Jonkers44,45, Alejandro Arias Vasquez26,63, Eco J C de Geus31,64, Katie A Meyer65,66, Jakob Stokholm23, Eran Segal22, Elin Org21, Cisca Wijmenga7, Hyung-Lae Kim67, Robert C Kaplan68, Tim D Spector9, Andre G Uitterlinden2,3,34, Fernando Rivadeneira2,3, Andre Franke17, Markus M Lerch16, Lude Franke7, Serena Sanna7,69, Mauro D'Amato13,70,71,72, Oluf Pedersen15, Andrew D Paterson73, Robert Kraaij2, Jeroen Raes4,5, Alexandra Zhernakova74.
Abstract
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.Entities:
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Year: 2021 PMID： 33462485 PMCID： PMC8515199 DOI： 10.1038/s41588-020-00763-1
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 41.307