AI Article Synopsis
- Polycystic ovary syndrome (PCOS) affects 5-15% of premenopausal women and is characterized by hormonal imbalances and ovarian abnormalities, with only a small part of its genetic basis understood so far.* -
- This study aimed to explore the role of rare genetic variants in the development of PCOS by analyzing DNA from 261 individuals across 62 families with affected daughters.* -
- The research identified significant associations between rare genetic variants in the DENND1A gene and reproductive/metabolic traits, supporting the idea that DENND1A is crucial to PCOS and suggesting that these rare variants influence the disease’s development.*
Article Abstract
Context: Polycystic ovary syndrome (PCOS) is among the most common endocrine disorders of premenopausal women, affecting 5% to15% of this population depending on the diagnostic criteria applied. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. PCOS is highly heritable, but only a small proportion of this heritability can be accounted for by the common genetic susceptibility variants identified to date.
Objective: The objective of this study was to test whether rare genetic variants contribute to PCOS pathogenesis.
Design, Patients, And Methods: We performed whole-genome sequencing on DNA from 261 individuals from 62 families with one or more daughters with PCOS. We tested for associations of rare variants with PCOS and its concomitant hormonal traits using a quantitative trait meta-analysis.
Results: We found rare variants in DENND1A (P = 5.31 × 10-5, adjusted P = 0.039) that were significantly associated with reproductive and metabolic traits in PCOS families.
Conclusions: Common variants in DENND1A have previously been associated with PCOS diagnosis in genome-wide association studies. Subsequent studies indicated that DENND1A is an important regulator of human ovarian androgen biosynthesis. Our findings provide additional evidence that DENND1A plays a central role in PCOS and suggest that rare noncoding variants contribute to disease pathogenesis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6660913 | PMC |
| http://dx.doi.org/10.1210/jc.2018-02496 | DOI Listing |
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