Association of host genome with intestinal microbial composition in a large healthy cohort.
Intestinal microbiota is known to be important in health and disease. Its composition is influenced by both environmental and host factors. Few large-scale studies have evaluated the association between host genetic variation and the composition of microbiota. We recruited a cohort of 1,561 healthy individuals, of whom 270 belong in 123 families, and found that almost one-third of fecal bacterial taxa were heritable. In addition, we identified 58 SNPs associated with the relative abundance of 33 taxa in 1,098 discovery subjects. Among these, four loci were replicated in a second cohort of 463 subjects: rs62171178 (nearest gene UBR3) associated with Rikenellaceae, rs1394174 (CNTN6) associated with Faecalibacterium, rs59846192 (DMRTB1) associated with Lachnospira, and rs28473221 (SALL3) associated with Eubacterium. After correction for multiple testing, 6 of the 58 associations remained significant, one of which replicated. These results identify associations between specific genetic variants and the gut microbiome.
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.|Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Williams
W
Turpin
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.|Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Osvaldo
O
Espin-Garcia
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Wei
W
Xu
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.|Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.|Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Mark S
MS
Silverberg
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.|Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
David
D
Kevans
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.|Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Michelle I
MI
Smith
Department of Cell and Systems Biology, University of Toronto, Toronto, Ontario, Canada.|Centre for the Analysis of Genome Evolution and Function, University of Toronto, Toronto, Ontario, Canada.
David S
DS
Guttman
Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Anne
A
Griffiths
Inflammatory Bowel Disease Clinic, Division of Gastroenterology and Hepatology, University of Calgary, Calgary, Alberta, Canada.
Remo
R
Panaccione
Departement of Pediatrics, IWK Health Centre, Halifax, Nova Scotia, Canada.
Anthony
A
Otley
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.|Genetics and Genome Biology, The Hospital for Sick Children Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Lizhen
L
Xu
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Konstantin
K
Shestopaloff
Department of Biology, Wilfrid Laurier University, Waterloo, Ontario, Canada.
Gabriel
0000-0002-2457-4450
G
Moreno-Hagelsieb
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.|Genetics and Genome Biology, The Hospital for Sick Children Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.|Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
Andrew D
AD
Paterson
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada.|Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.|Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Kenneth
K
Croitoru
D000293:Adolescent; D001419:Bacteria / Q000145:classification; D015331:Cohort Studies; D005260:Female; D000069196:Gastrointestinal Microbiome; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult