A kaleidoscopic view of ovarian genes associated with polycystic ovary syndrome

Systematic Review

VOLUME 2, ISSUE 4, P330-341, OCTOBER 01, 2021


Sezcan Mumusoglu, M.D., Qingling Yang, Ph.D., Aaron J. Hsueh, Ph.D. 


Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder affecting 6%–10% of reproductive-age women, and it is associated with defects in follicle functions. On the basis of advances in the evaluation of gene variants, together with family-based and genome-wide association studies, we discussed genes associated with PCOS. We used a gene-centric approach to sort out literature deposited in the Ovarian Kaleidoscope database (http://okdb.appliedbioinfo.net) by subcategorizing candidate genes as ligand-receptor signaling, meiosis and deoxyribonucleic acid repair, transcriptional factors, ribonucleic acid metabolism, enzymes, and others. Although multiple individual candidate genes with single nucleotide polymorphisms have been identified in patients with PCOS, only a limited number of findings have been verified and deal with genes with known ovarian functions. On the basis of genome-wide association studies, a limited group of PCOS candidate genes, including FSHB, FSHR, LHR, YAP1, AOPEP/C9orf3, RAB5/SUOX, THADA, and DENND1A, yielded consistent association in good-quality studies in both Caucasian and Chinese populations. Although some of these genes have known ovarian functions, the ovarian expression and function of others remain to be elucidated. Overall, PCOS candidate genes are likely associated with abnormal gene expression because of their recent evolutionary origins. Studying rare variants in complex diseases such as PCOS presents unique challenges. The identification of rare variants and functional gene networks by next-generation sequencing along with epigenetic studies may increase our understanding of the genetic bases of PCOS. A better definition of unique diseases underlying PCOS on the basis of ovarian expression patterns could provide new diagnosis and treatments.

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