4.8 Article

Association of host genome with intestinal microbial composition in a large healthy cohort

Journal

NATURE GENETICS
Volume 48, Issue 11, Pages 1413-1417

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3693

Keywords

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Funding

  1. Crohn's and Colitis Canada
  2. Canadian Institutes of Health Research (CIHR) [CMF108031]
  3. Helmsley Charitable Trust
  4. Postdoctoral Fellowship Research Award from CIHR Fellowship/Canadian Association of Gastroenterology (CAG)/Ferring Pharmaceuticals, Inc.
  5. Department of Medicine, Mount Sinai Hospital, Toronto
  6. Gale and Graham Wright Chair in Digestive Diseases
  7. CIHR/CAG/Abbvie IBD Fellowship Award
  8. CIHR STAGE fellowship
  9. Ontario Graduate Scholarship

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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.

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