Characterizing Variation in Sex Steroid Hormone Pathway Genes in Women of 4 Races/Ethnicities: The Study of Women’s Health Across the Nation (SWAN)

Abstract This report characterizes genotypes and haplotypes in 6 genes (27 single nucleotide polymorphisms [SNPs]) from the Sex Steroid Hormone Genetics Protocol developed though the DNA Repository of the Study of Women's Health Across the Nation (SWAN) Genetics Study. The SWAN Genetics Study is a component of a longitudinal study describing health-related attributes of the menopausal transition in African American, Caucasian, Chinese, Hispanic, and Japanese women. At baseline, SWAN recruited menstruating women, aged 42 to 52 years, who were not using exogenous hormones. During the sixth and seventh years of the study, buccal cells in a mouthwash slurry and whole blood were collected for a DNA repository. Immortalized cell lines were created and genotyped in 1,538 specimens from 1,757 women who participated in the SWAN Genetics Study. DNA from those cells was genotyped for genes in the sex steroid hormone pathway. SNPs were evaluated for genotype and allele frequencies (and differences) according to race/ethnicity and haplotyped in anticipation of studying their associations with health-related measures. We demonstrated that allele frequencies differed significantly by race/ethnicity. There was substantial linkage disequilibrium among many of the SNPs and only a few SNPs showed significant Hardy-Weinberg disequilibrium within race/ethnicity. Finally, there are a number of haplotype patterns that vary according to race/ethnicity, including a "yin-yang" pattern for 17HSD among Caucasian, Chinese, and Japanese women, but not among African American women. Repository specimens developed in anticipation of genomic or metabolomics studies can extend the contribution of the parent study by developing hybrid strategies that support both SNP association studies as well as coarse and fine mapping to evaluate possible genomic locations of causal variants.