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

Ambalavanan A.; Chang L.; Choi J.; Zhang Y.; Stickley S.A.; Fang Z.Y.; Miliku K.; Robertson B.; Yonemitsu C.; Turvey S.E.; Mandhane P.J.; Simons E.; Moraes T.J.; Anand S.S.; Paré G.; Williams J.E.; Murdoch B.M.; Otoo G.E.; Mbugua S.; Kamau-Mbuthia E.W.; Kamundia E.W.; Gindola D.K.; Rodriguez J.M.; Pareja R.G.; Sellen D.W.; Moore S.E.; Prentice A.M.; Foster J.A.; Kvist L.J.; Neibergs H.L.; McGuire M.A.; McGuire M.K.; Meehan C.L.; Sears M.R.; Subbarao P.; Azad M.B.; Bode L.; Duan Q. · Nature Communications (2024) · DOI: 10.1038/s41467-024-51743-6

Resumen

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 < 0.01). Thus, we report novel genetic factors associated with HMOs, some of which may protect the respiratory health of children. © The Author(s) 2024.