Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
School of Computing, Queen's University, Kingston, ON, Canada.
Nat Commun. 2024 Sep 4;15(1):7735. doi: 10.1038/s41467-024-51743-6.
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.
母乳喂养有诸多健康益处，但它对呼吸道健康的影响尚不清楚。本研究通过调查调节人乳低聚糖（HMO）的母体基因组因素及其与人乳喂养婴儿呼吸道健康的关系，解决了母婴-婴儿三元体的复杂和动态性质。从 CHILD 队列研究的 980 位母亲中定量了 19 种 HMO。全基因组关联研究鉴定了染色体 19p13.3 和 19q13.33 上与 HMO 相关的位点（最低 P=2.4e-118），跨越了几个岩藻糖基转移酶（FUT）基因。我们在 3q27.3 上发现了 6'-唾液酸乳糖的新关联（P=2.2e-9），位于唾液酸转移酶（ST6GAL1）基因中。这些关联，加上在染色体 7q21.32、7q31.32 和 13q33.3 上的其他关联，在独立的 INSPIRE 队列中得到了复制。此外，基因-环境相互作用分析表明，岩藻糖基 HMO 可能调节具有不同遗传风险评分的学龄前儿童反复喘息的总体风险（P<0.01）。因此，我们报告了与 HMO 相关的新的遗传因素，其中一些可能保护儿童的呼吸道健康。
