Multivariate, region‐based genetic analyses of facets of reproductive aging in White and Black women

BACKGROUND: Age at final menstrual period (FMP) and the accompanying hormone trajectories across the menopause transition do not occur in isolation, but likely share molecular pathways. Understanding the genetics underlying the endocrinology of the menopause transition may be enhanced by jointly analyzing multiple interrelated traits. METHODS: In a sample of 347 White and 164 Black women from the Study of Women's Health Across the Nation (SWAN), we investigated pleiotropic effects of 54 candidate genetic regions of interest (ROI) on 5 menopausal traits (age at FMP and premenopausal and postmenopausal levels of follicle stimulation hormone and estradiol) using multivariate kernel regression (Multi‐SKAT). A backward elimination procedure was used to identify which subset of traits were most strongly associated with a specific ROI. RESULTS: In White women, the 20 kb ROI around rs10734411 was significantly associated with the multivariate distribution of age at FMP, premenopausal estradiol, and postmenopausal estradiol (omnibus p‐value = .00004). This association did not replicate in the smaller sample of Black women. CONCLUSION: This study using a region‐based, multiple‐trait approach suggests a shared genetic basis among multiple facets of reproductive aging.