TY - JOUR
T1 - Large-scale association analyses identify host factors influencing human gut microbiome composition
AU - MiBioGen Consortium Initiative
AU - Kurilshikov, Alexander
AU - Medina-Gomez, Carolina
AU - Bacigalupe, Rodrigo
AU - Radjabzadeh, Djawad
AU - Wang, Jun
AU - Demirkan, Ayse
AU - Le Roy, Caroline I.
AU - Raygoza Garay, Juan Antonio
AU - Finnicum, Casey T.
AU - Liu, Xingrong
AU - Zhernakova, Daria V.
AU - Bonder, Marc Jan
AU - Hansen, Tue H.
AU - Frost, Fabian
AU - Rühlemann, Malte C.
AU - Turpin, Williams
AU - Moon, Jee Young
AU - Kim, Han Na
AU - Lüll, Kreete
AU - Barkan, Elad
AU - Shah, Shiraz A.
AU - Fornage, Myriam
AU - Szopinska-Tokov, Joanna
AU - Wallen, Zachary D.
AU - Borisevich, Dmitrii
AU - Agreus, Lars
AU - Andreasson, Anna
AU - Bang, Corinna
AU - Bedrani, Larbi
AU - Bell, Jordana T.
AU - Bisgaard, Hans
AU - Boehnke, Michael
AU - Boomsma, Dorret I.
AU - Burk, Robert D.
AU - Claringbould, Annique
AU - Croitoru, Kenneth
AU - Davies, Gareth E.
AU - van Duijn, Cornelia M.
AU - Duijts, Liesbeth
AU - Falony, Gwen
AU - Fu, Jingyuan
AU - van der Graaf, Adriaan
AU - Hansen, Torben
AU - Homuth, Georg
AU - Hughes, David A.
AU - Ijzerman, Richard G.
AU - Jackson, Matthew A.
AU - Watanabe, Kyoko
AU - Willemsen, Gonneke
AU - de Geus, Eco J.C.
AU - Jaddoe, Vincent W. V.
AU - Joossens, Marie
AU - Jørgensen, Torben
AU - Keszthelyi, Daniel
AU - Knight, Rob
AU - Laakso, Markku
AU - Laudes, Matthias
AU - Launer, Lenore J.
AU - Lieb, Wolfgang
AU - Lusis, Aldons J.
AU - Masclee, Ad A. M.
AU - Moll, Henriette A.
AU - Mujagic, Zlatan
AU - Qibin, Qi
AU - Rothschild, Daphna
AU - Shin, Hocheol
AU - Sørensen, S. ren J.
AU - Steves, Claire J.
AU - Thorsen, Jonathan
AU - Timpson, Nicholas J.
AU - Tito, Raul Y.
AU - Vieira-Silva, Sara
AU - Völker, Uwe
AU - Völzke, Henry
AU - Võsa, Urmo
AU - Wade, Kaitlin H.
AU - Walter, Susanna
AU - Weiss, Stefan
AU - Weiss, Frank U.
AU - Weissbrod, Omer
AU - Westra, Harm-Jan
AU - Payami, Haydeh
AU - Jonkers, Daisy M. A. E.
AU - Arias Vasquez, Alejandro
AU - Meyer, Katie A.
AU - Stokholm, Jakob
AU - Segal, Eran
AU - Org, Elin
AU - Wijmenga, Cisca
AU - Kim, Hyung-Lae
AU - Kaplan, Robert C.
AU - Spector, Tim D.
AU - Uitterlinden, Andre G.
AU - Rivadeneira, Fernando
AU - Franke, Andre
AU - Lerch, Markus M.
AU - Franke, Lude
AU - Sanna, Serena
AU - D’Amato, Mauro
AU - Pedersen, Oluf
AU - Paterson, Andrew D.
AU - Kraaij, Robert
AU - Raes, Jeroen
AU - Zhernakova, Alexandra
N1 - Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85100210047&partnerID=8YFLogxK
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UR - https://www.ncbi.nlm.nih.gov/pubmed/33462485
U2 - https://doi.org/10.1038/s41588-020-00763-1
DO - https://doi.org/10.1038/s41588-020-00763-1
M3 - Article
C2 - 33462485
SN - 1061-4036
VL - 53
SP - 156
EP - 165
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -