The effect of host genetics on the gut microbiome.
The gut microbiome is affected by multiple factors, including genetics. In this study, we assessed the influence of host genetics on microbial species, pathways and gene ontology categories, on the basis of metagenomic sequencing in 1,514 subjects. In a genome-wide analysis, we identified associations of 9 loci with microbial taxonomies and 33 loci with microbial pathways and gene ontology terms at P < 5 × 10-8. Additionally, in a targeted analysis of regions involved in complex diseases, innate and adaptive immunity, or food preferences, 32 loci were identified at the suggestive level of P < 5 × 10-6. Most of our reported associations are new, including genome-wide significance for the C-type lectin molecules CLEC4F-CD207 at 2p13.3 and CLEC4A-FAM90A1 at 12p13. We also identified association of a functional LCT SNP with the Bifidobacterium genus (P = 3.45 × 10-8) and provide evidence of a gene-diet interaction in the regulation of Bifidobacterium abundance. Our results demonstrate the importance of understanding host-microbe interactions to gain better insight into human health.
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Marc Jan
MJ
Bonder
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.|Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia.|Department of Natural Sciences, Novosibirsk State University, Novosibirsk, Russia.
Alexander
0000-0003-2541-5627
A
Kurilshikov
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.|Top Institute Food and Nutrition, Wageningen, the Netherlands.
Ettje F
EF
Tigchelaar
Top Institute Food and Nutrition, Wageningen, the Netherlands.|Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.
Zlatan
Z
Mujagic
University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, the Netherlands.
Floris
F
Imhann
University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, the Netherlands.
Arnau Vich
AV
Vila
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands.
Patrick
0000-0002-5654-3966
P
Deelen
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Computer Science, Aalto University School of Science, Espoo, Finland.
Tommi
T
Vatanen
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Melanie
M
Schirmer
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.|Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Sanne P
SP
Smeekens
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Daria V
DV
Zhernakova
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, the Netherlands.
Soesma A
0000-0001-9225-9236
SA
Jankipersadsing
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.|Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Martin
M
Jaeger
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.|Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Marije
M
Oosting
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Maria Carmen
MC
Cenit
Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.
Ad A M
AA
Masclee
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Genomics Coordination Center, Groningen, the Netherlands.
Morris A
MA
Swertz
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Yang
Y
Li
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Vinod
V
Kumar
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.|Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Leo
L
Joosten
University of Groningen, University Medical Center Groningen, Department of Medical Microbiology, Groningen, the Netherlands.
Hermie
H
Harmsen
University of Groningen, University Medical Center Groningen, Department of Gastroenterology and Hepatology, Groningen, the Netherlands.
Rinse K
RK
Weersma
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Lude
0000-0002-5159-8802
L
Franke
University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, the Netherlands.
Marten H
MH
Hofker
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.|Center for Computational and Integrative Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.|Gastrointestinal Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.|Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ramnik J
RJ
Xavier
Division of Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.
Daisy
D
Jonkers
Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.|Radboud Center of Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Mihai G
MG
Netea
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.
Cisca
C
Wijmenga
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.|University of Groningen, University Medical Center Groningen, Department of Pediatrics, Groningen, the Netherlands.
Jingyuan
J
Fu
University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.|Top Institute Food and Nutrition, Wageningen, the Netherlands.
Alexandra
0000-0002-4574-0841
A
Zhernakova
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015331:Cohort Studies; D005260:Female; D000069196:Gastrointestinal Microbiome; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007109:Immunity / Q000235:genetics; D008297:Male; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult