HealthDay News — Rare variants have been identified in the DENND1A gene that are associated with hormonal traits of polycystic ovary syndrome (PCOS), according to research published online April 30 in the Journal of Clinical Endocrinology & Metabolism.
Matthew Dapas, from the Northwestern University Feinberg School of Medicine in Chicago, and colleagues performed whole-genome sequencing on DNA from 261 individuals from 62 families with at least one daughter with PCOS. Using a quantitative trait meta-analysis, associations of rare variants with PCOS and its concomitant hormonal traits were examined.
The researchers identified rare variants in DENND1A. In PCOS families, these variants were significantly associated with reproductive and metabolic traits.
“In summary, by applying family-based sequence kernel association tests on filtered whole-genome variant call data from a cohort of PCOS families, we were able to identify rare variants in the DENND1A gene that were associated with quantitative hormonal traits of PCOS,” the authors write. “Since DENND1A is an important regulator of androgen biosynthesis, these findings provide additional genetic evidence to support our hypothesis that hyperandrogenemia is a core biologic pathway in PCOS. Our results also suggest that rare noncoding variants contribute to the distinctive hormonal profile of PCOS.”