Abstract
OBJECTIVE: To determine whether European Americans with polycystic ovary syndrome (PCOS) exhibit genetic differences associated with PCOS status and phenotypic features. DESIGN: Case-control association study in European Americans. SETTING: Academic center. SUBJECT(S): Women with PCOS diagnosed with the use of the National Institutes of Health criteria (n = 532) and control women with regular menstrual cycles and no evidence of hyperandrogenism (n = 432). INTERVENTION(S): Blood was drawn for measurement of sex steroids, metabolic parameters, and genotyping. MAIN OUTCOME MEASURE(S): Associations among PCOS status, phenotype, and genetic background identified with the use of principal component analysis. RESULT(S): Principal component analysis identified five principal components (PCs). PC1 captured northwest-to-southeast European genetic variation and was associated with PCOS status. Acanthosis was associated with southern European ancestry, and larger waist:hip ratio was associated with northern European ancestry. PC2 was associated with east-to-west European genetic variation and cholesterol levels. CONCLUSION(S): These data provide evidence for genetic influence based on European ethnicity in women with PCOS. There is also evidence for a genetic component in the phenotypic features of PCOS within a mixed European population. The data point to the need to control for population stratification in genetic studies in women of mixed European ethnicity. They also emphasize the need for better studies of PCOS prevalence and phenotype as a function of genetic background.