{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:28:06Z","timestamp":1787066886973,"version":"build-2736575974"},"posted":{"date-parts":[[2026,8,14]]},"group-title":"Genomics","reference-count":92,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01HD109830"],"award-info":[{"award-number":["R01HD109830"]}]},{"name":"NIH","award":["R35GM124676"],"award-info":[{"award-number":["R35GM124676"]}]},{"name":"NIH","award":["R01HD080444"],"award-info":[{"award-number":["R01HD080444"]}]},{"name":"NIH","award":["R00HD113834"],"award-info":[{"award-number":["R00HD113834"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Human milk contains a diverse array of metabolites that contribute to infant nutrition, immune development, and microbial colonization. The maternal factors shaping the milk metabolome, and the relative contribution of genetics or diet vs. other factors, remain poorly understood. Here, we profiled 458 milk metabolites in 349 one-month postpartum human milk samples and integrated metabolomic data with maternal diet, clinical, transcriptomic, and genomic measurements. Maternal diet was broadly associated with milk metabolite composition, with significant correlations identified between dietary features and 323 metabolites. Coffee consumption strongly predicted milk quinic acid and 1,3-dimethyluric acid abundance, while high-fiber dietary patterns were associated with metabolites including proline-betaine and N-acetylornithine. Integration of milk transcriptomic and metabolomic data via machine learning identified biologically plausible gene-metabolite pairs, including associations between\n                  <jats:italic>QPRT<\/jats:italic>\n                  expression and quinolinic acid, and\n                  <jats:italic>DPEP1<\/jats:italic>\n                  and cysteine-glycine dipeptide. Genome-wide association analyses identified nine study-wide significant metabolite quantitative trait loci, including novel milk-specific associations near\n                  <jats:italic>PDE6A<\/jats:italic>\n                  affecting purine metabolites and near\n                  <jats:italic>GNE<\/jats:italic>\n                  affecting free sialic acid. Comparison with plasma metabolite studies demonstrated both shared and milk-specific genetic regulation of metabolites. Finally, we found that of all tested maternal features, diet explained the largest proportion of variation in the milk metabolome. Together, these findings demonstrate that the human milk metabolome reflects both maternal exposures and mammary gland-specific biology. This work establishes a framework for understanding how genetic and environmental factors shape milk composition.\n                <\/jats:p>","DOI":"10.64898\/2026.08.11.744248","type":"posted-content","created":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T05:50:13Z","timestamp":1786773013000},"source":"Crossref","is-referenced-by-count":0,"title":["Maternal diet and genetics shape the human milk metabolome"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9180-6381","authenticated-orcid":false,"given":"Kelsey E.","family":"Johnson","sequence":"first","affiliation":[{"name":"Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Duan","sequence":"additional","affiliation":[{"name":"Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Youssef","sequence":"additional","affiliation":[{"name":"Chan School of Medicine, University of Massachusetts, Worcester, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J","family":"Aristizabal-Henao","sequence":"additional","affiliation":[{"name":"BPGbio, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Johnson","sequence":"additional","affiliation":[{"name":"Riddet Institute, Massey University, Turitea, NZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A.","family":"Kiebish","sequence":"additional","affiliation":[{"name":"BPGbio, Waltham, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily M.","family":"Nagel","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Palmsten","sequence":"additional","affiliation":[{"name":"Pregnancy and Child Health Research Center, HealthPartners Institute, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Pierce","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Wernimont","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Gynecology, and Women\u2019s Health, University of Minnesota Medical School, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Bode","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Larsson-Rosenquist Foundation Mother-Milk-Infant Center of Research Excellence, and the Human Milk Institute, University of California San Diego."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric F.","family":"Lock","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, University of Minnesota School of Public Health, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira M.","family":"Isganaitis","sequence":"additional","affiliation":[{"name":"Joslin Diabetes Center and Department of Pediatrics, Harvard Medical School, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Fields","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank W.","family":"Albert","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Blekhman","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Chicago, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen W.","family":"Demerath","sequence":"additional","affiliation":[{"name":"Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081807201143000_2026.08.11.744248v1.1","doi-asserted-by":"crossref","unstructured":"Majood, M. & Rao, R . 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