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

Ambalavanan, A; Chang, LORCID logo; Choi, J; Zhang, Y; Stickley, SAORCID logo; Fang, ZY; Miliku, K; Robertson, B; Yonemitsu, C; Turvey, SE; +28 more...Mandhane, PJ; Simons, E; Moraes, TJ; Anand, SSORCID logo; Paré, GORCID logo; Williams, JEORCID logo; Murdoch, BMORCID logo; Otoo, GE; Mbugua, S; Kamau-Mbuthia, EW; Kamundia, EW; Gindola, DK; Rodriguez, JM; Pareja, RG; Sellen, DW; Moore, SE; Prentice, AMORCID logo; Foster, JA; Kvist, LJ; Neibergs, HL; McGuire, MA; McGuire, MKORCID logo; Meehan, CL; Sears, MR; Subbarao, PORCID logo; Azad, MBORCID logo; Bode, LORCID logo; Duan, QORCID logo and (2024) Human milk oligosaccharides are associated with maternal genetics and respiratory health of human milk-fed children. Nature communications, 15 (1). 7735-. ISSN 2041-1723 DOI: 10.1038/s41467-024-51743-6
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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.


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