Sex steroid hormone pathway genes and health-related measures in women of 4 races/ethnicities: the Study of Women's Health Across the Nation (SWAN).
We synthesized findings relating health outcomes and genetic variants of the sex steroid hormone pathway in women from the Study of Women's Health Across the Nation (SWAN) Genetics Study. The SWAN Genetics Study, a component of the longitudinal SWAN study, describes selected genetics characteristics of health-related attributes during the menopausal transition in African American, Caucasian, Chinese, and Japanese women. At baseline, SWAN recruited menstruating women aged 42 to 52 years, who were not using exogenous hormones. Immortalized cell lines were developed and genotyped in 1,538 specimens from 1,757 participants in the genetics study. Genotypes and haplotypes from 6 genes (27 single nucleotide polymorphisms [SNPs]) in the sex steroid hormone pathway were related to circulating hormone concentrations, menstrual cycle profiles, and health-related outcomes, including lipids, diabetes mellitus, depressive symptoms, measures of cognition, bone mineral density (BMD), and vasomotor symptoms. Allele frequencies and distances differed substantially in the 4 race/ethnicity-specific groups evaluated, leading to variable patterns of association with health-related measures. For example, 17HSD genotypes were highly associated with diabetes risk in Caucasian women, whereas its haplotypes were associated with diabetes risk in both African American and Caucasian women. Several SNPs were associated with multiple outcomes. ESR1 rs3798577 was significantly associated with circulating estradiol concentrations, indicators of ovarian aging, high-density lipoprotein (HDL) cholesterol, apolipoprotein A-1, insulin sensitivity, and lumbar spine BMD. CYP1A1 rs2606345 was related to estrogen metabolite concentrations, vasomotor symptoms, and depressive symptoms. Some associations were much more prominent in specific races/ethnicities; Chinese women had statistically significant relations between ESR2 rs1256030 and HDL cholesterol, lumbar spine BMD, hip BMD, and metabolic syndrome. Importantly, women in the SWAN Genetics Study were typical of women in the community-based SWAN sample. This community-based sample of women from the SWAN Genetics Study identified important genetic sex steroid hormone pathway variants in relation to measures of health status. The magnitude and breadth of these relationships should motivate further research to verify and extend the findings.
Sowers
MaryFran R
MR
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan 48104, USA. mfsowers@umich.edu
Wilson
Angela L
AL
Karvonen-Gutierrez
Carrie A
CA
Kardia
Sharon R
SR
D000328:Adult; D005260:Female; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006306:Health Surveys; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups / Q000235:genetics*
D012739:Gonadal Steroid Hormones