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Title: Title: Human milk variation is shaped by maternal genetics and impacts the infant gut microbiome 1 2 Authors: 3 4 Kelsey E

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DOI: 10.1101/2023.01.24.525211

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Abstract: 34 Human milk is a complex mix of nutritional and bioactive components that provide complete nutrition for 35 the infant. However, we lack a systematic knowledge of the factors shaping milk composition and how 36 milk variation influences infant health. Here, we used multi-omic profiling to characterize interactions 37 between maternal genetics, milk gene expression, milk composition, and the infant fecal microbiome in 38 242 exclusively breastfeeding mother-infant pairs. We identified 487 genetic loci associated with milk 39 gene expression unique to the lactating mammary gland, including loci that impacted breast cancer risk 40 and human milk oligosaccharide concentration. Integrative analyses uncovered connections between 41 milk gene expression and infant gut microbiome, including an association between the expression of 42 inflammation-related genes with IL-6 concentration in milk and the abundance of Bifidobacteria in the 43 infant gut. Our results show how an improved understanding of the genetics and genomics of human 44 milk connects lactation biology with maternal and infant health. 45 46. CC-BY 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made The copyright holder for this preprint this version posted January 25, 2023. ; https://doi.

Url: https://doi.org/10.1101/2023.01.24.525211

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Authors: Heisel, Timothy; Allert, Mattea; Fürst, Annalee; Yerabandi, Nikhila; Knights, Dan; Jacobs, Katherine M; Lock, Eric F; Bode, Lars; Fields, David A; Rudolph, Michael C; Albert, Frank W; Demerath, Ellen W; Blekhman, Ran

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