re associated with VMS in a multiracial/ethnic cohort.Methods: For 702 White, 306 Black, 126 Chinese, and 129 Japanese women from the Study of Women\’s Health Across the Nation (SWAN) Genomic Substudy, we created polygenic risk scores (PRSs) from genome-wide association studies of VMS and ages at menarche and menopause. PRSs and single nucleotide polymorphisms (SNPs) from a previously identified VMS locus (tachykinin receptor 3 [TACR3]) were evaluated for associations with frequent VMS (VMS ≥6 days in the past 2 weeks at any visit) and with VMS trajectories (persistently low, early onset, final menstrual period onset, persistently high).Results: The C-allele of rs74827081 in TACR3 was associated with reduced likelihood of frequent VMS in White women (odds ratio [OR] = 0.49 [95% CI, 0.29-0.83]). With higher menarche PRS (later menarche), Black women were less likely (OR = 0.55 [95% CI, 0.38-0.78]) to report frequent VMS. With higher PRS for age at menarche, Black women were also less likely to have a persistently high VMS trajectory (OR = 0.55 [95% CI, 0.34-0.91]), whereas White women (OR = 0.75 [95% CI, 0.58-0.98]) were less likely to have a final menstrual period onset trajectory (vs persistently low). Chinese women with higher menopause PRS were more likely to have frequent VMS (OR = 2.29 [95% CI, 1.39-3.78]). Associations were substantively similar after excluding rs74827081 C-allele carriers.Conclusions: Genetic factors predictive of reproductive aging are also associated with VMS, suggesting that VMS have a polygenic architecture. Further study in this area may help to identify new targets for novel VMS therapies.Video Summary:http://links.lww.com/MENO/A761.Address correspondence to: Sioban D. Harlow, PhD, Department of Epidemiology, University of Michigan, 1415 Washington Heights, Suite 6610, Ann Arbor MI 48109-2029. E-mail: [email protected] 15 December, 2020Revised 8 March, 2021Accepted 8 March, 2021W.Z. and J.A.S. contributed equally to this manuscript.Funding/support: The Study of Women\’s Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women\’s Health (ORWH) (Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495), and for the SWAN Genomic Analyses an SWAN Legacy (U01AG017719). The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH, or the NIH. S.D.H. gratefully acknowledge use of the services and facilities of the Population Studies Center at the University of Michigan, funded by NICHD Center Grant R24 HD041028.Financial disclosure/conflicts of interest: RCT: Consulting/Advisory Board: Astellas, Pfizer, Procter & Gamble, Virtue Health. No disclosures for W.Z., J.A.S,. P.A.P., C.J.C., E.R.-N., M.Y., M.M.H., S.L.R.K., S.D.H., and C.J.C.Supplemental digital content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal\’s Website (www.menopause.org).? 2021 by The North American Menopause Society….