{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:03:42Z","timestamp":1789657422026,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,13]]},"group-title":"Epidemiology","reference-count":59,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:00:00Z","timestamp":1789257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["R01AG051600"],"award-info":[{"award-number":["R01AG051600"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["ZIAAG000530"],"award-info":[{"award-number":["ZIAAG000530"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]},{"name":"USDA\/ARS","award":["58-3092-5-001"],"award-info":[{"award-number":["58-3092-5-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>Psychological distress is associated with metabolic alterations that contribute to adverse cardiometabolic outcomes across diverse populations. We previously developed a metabolite-based distress score (MDS) in predominantly White women. Because men and Black individuals suffer high rates of cardiometabolic disease, we evaluated whether the MDS is similarly associated with depression in these populations, and derived a multi-ethnic MDS (MDS-ME) among Black individuals with replications in independent samples.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Data were from three U.S. cohorts, the Multi-Ethnic Study of Atherosclerosis (MESA), Women\u2019s Health Initiative (WHI), and Nurses\u2019 Health Study (NHS), evaluated in 4 stages. Stages 1-3 included 2,477 White and 1,625 Black MESA participants with depression status data and plasma metabolomics assessed at baseline. Stage 1: We calculated the MDS and examined its association with depression status. Stage 2: We conducted an agnostic analysis among a 70% random subset of Black participants to identify additional relevant metabolites. Stage 3: We derived an MDS-ME in Black participants. Stage 4: We evaluated the MDS-ME using independent samples from all three cohorts.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The previously validated 20-metabolite MDS showed stronger associations with prevalent depression in White (OR: 1.93, 95% CI: 1.71, 2.19) versus Black (OR: 1.13, 95% CI: 0.97, 1.33) MESA participants. Associations were generally similar in men and women. The MDS-ME comprised 33 metabolites, and relative to the MDS was more strongly associated with depression in Black participants (OR: 1.45; 95% CI: 1.04, 2.03), with associations also evident in White participants (OR: 1.81; 95% CI: 1.60, 2.04). The MDS-ME was similarly associated with depression in Black women in WHI and NHS.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Results suggest that incorporating metabolites identified in Black participants enhances the utility and generalizability of the MDS across more diverse populations.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.10.26362734","type":"posted-content","created":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T21:45:11Z","timestamp":1789335911000},"source":"Crossref","is-referenced-by-count":0,"title":["Assessing and refining a metabolite-based distress score for use in different populations within three US cohorts"],"prefix":"10.64898","author":[{"given":"Tianyi","family":"Huang","sequence":"first","affiliation":[{"name":"Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiwen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raji","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea L.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8259-9245","authenticated-orcid":false,"given":"Clary B.","family":"Clish","sequence":"additional","affiliation":[{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Avila-Pacheco","sequence":"additional","affiliation":[{"name":"Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome I.","family":"Rotter","sequence":"additional","affiliation":[{"name":"The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuqing","family":"Guo","sequence":"additional","affiliation":[{"name":"The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yao","sequence":"additional","affiliation":[{"name":"The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yii-Der Ida","family":"Chen","sequence":"additional","affiliation":[{"name":"The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen S.","family":"Rich","sequence":"additional","affiliation":[{"name":"Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent D.","family":"Taylor","sequence":"additional","affiliation":[{"name":"The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis C.","family":"Wood","sequence":"additional","affiliation":[{"name":"USDA\/ARS Children\u2019s Nutrition Research Center, Baylor College of Medicine, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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