Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children

Ambalavanan A 1 , Chang L 1 , Choi J 1 , Zhang Y 2 , Stickley SA 1 , Fang ZY 1 Show all authors , Miliku K 3 , Robertson B 4 , Yonemitsu C 4 , Turvey SE 5 , Mandhane PJ 6 , Simons E 7 , Moraes TJ 8 , Anand SS 9 , Paré G 10 , Williams JE 11 , Murdoch BM 11 , Otoo GE 12 , Mbugua S 13 , Kamau-Mbuthia EW 13 , Kamundia EW 13 , Gindola DK 14 , Rodriguez JM 15 , Pareja RG 16 , Sellen DW 17 , Moore SE 18 , Prentice AM 19 , Foster JA 20 , Kvist LJ 21 , Neibergs HL 22 , McGuire MA 11 , McGuire MK 23 , Meehan CL 24 , Sears MR 3 , Subbarao P 3 , Azad MB 25 , Bode L 26 , Duan Q 27

Affiliations 

  • 1 Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada
  • 2 School of Computing, Queen's University, Kingston, ON, Canada
  • 3 Department of Medicine, McMaster University, Hamilton, ON, Canada
  • 4 Department of Pediatrics and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), Human Milk Institute (HMI), University of California San Diego, La Jolla, CA, USA
  • 5 Department of Pediatrics, Division of Allergy and Immunology, University of British Columbia, Vancouver, BC, Canada
  • 6 Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
  • 7 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada
  • 8 Department of Pediatrics, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada
  • 9 Chanchlani Research Centre, Dept. of Medicine, McMaster University, Hamilton, ON, Canada
  • 10 Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
  • 11 Department of Animal, Veterinary and Food Sciences, University of Idaho, Moscow, Idaho, USA
  • 12 Department of Nutrition & Food Science, University of Ghana, Accra, Ghana
  • 13 Department of Human Nutrition, Egerton University, Nakuru, Kenya
  • 14 Department of Anthropology, Hawassa University, Hawassa, Ethiopia
  • 15 Department of Nutrition and Food Science, Complutense University of Madrid, Madrid, Spain
  • 16 Nutrition Research Institute, Lima, Peru
  • 17 Department of Anthropology, University of Toronto, Toronto, ON, Canada
  • 18 Department of Women and Children's Health, King's College London, London, UK
  • 19 The Medical Research Council Unit, The Gambia at the London School of Hygiene & Tropical Medicine, Fajara, Gambia
  • 20 Department of Biological Sciences, University of Idaho, Moscow, ID, USA
  • 21 Faculty of Medicine, Lund University, Lund, Sweden
  • 22 Department of Animal Sciences, Washington State University, Pullman, WA, USA
  • 23 Margaret Ritchie School of Family and Consumer Sciences, University of Idaho, Moscow, ID, USA
  • 24 Department of Anthropology, Washington State University, Pullman, WA, USA
  • 25 Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada. [email protected]
  • 26 Department of Pediatrics and Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence (MOMI CORE), Human Milk Institute (HMI), University of California San Diego, La Jolla, CA, USA. [email protected]
  • 27 Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada. [email protected]
Nat Commun, 2024 Sep 04;15(1):7735.
PMID: 39232002 DOI: 10.1038/s41467-024-51743-6

Abstract

Breastfeeding provides many health benefits, but its impact on respiratory health remains unclear. This study addresses the complex and dynamic nature of the mother-milk-infant triad by investigating maternal genomic factors regulating human milk oligosaccharides (HMOs), and their associations with respiratory health among human milk-fed infants. Nineteen HMOs are quantified from 980 mothers of the CHILD Cohort Study. Genome-wide association studies identify HMO-associated loci on chromosome 19p13.3 and 19q13.33 (lowest P = 2.4e-118), spanning several fucosyltransferase (FUT) genes. We identify novel associations on chromosome 3q27.3 for 6'-sialyllactose (P = 2.2e-9) in the sialyltransferase (ST6GAL1) gene. These, plus additional associations on chromosomes 7q21.32, 7q31.32 and 13q33.3, are replicated in the independent INSPIRE Cohort. Moreover, gene-environment interaction analyses suggest that fucosylated HMOs may modulate overall risk of recurrent wheeze among preschoolers with variable genetic risk scores (P 

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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