title: Functional genomics of PCOS: from GWAS to molecular mechanisms.
abstract: Polycystic ovary syndrome (PCOS) is a common endocrinopathy characterized by increased ovarian androgen biosynthesis, anovulation, and infertility. PCOS has a strong heritable component based on familial clustering and twin studies. Genome-wide association studies (GWAS) identified several PCOS candidate loci including LHCGR, FSHR, ZNF217, YAP1, INSR, RAB5B, and C9orf3. We review the functional roles of strong PCOS candidate loci focusing on FSHR, LHCGR, INSR, and DENND1A. We propose that these candidates comprise a hierarchical signaling network by which DENND1A, LHCGR, INSR, RAB5B, adapter proteins, and associated downstream signaling cascades converge to regulate theca cell androgen biosynthesis. Future elucidation of the functional gene networks predicted by the PCOS GWAS will result in new diagnostic and therapeutic approaches for women with PCOS.
authors.affiliation: Department of Pathology, Penn State Hershey College of Medicine, Hershey, PA, USA; Department of Obstetrics and Gynecology, Penn State Hershey College of Medicine, Hershey, PA, USA. Electronic address: jmcallister@psu.edu.
authors.forename: Jan M
authors.initials: JM
authors.lastname: McAllister
authors.affiliation: Department of Obstetrics and Gynecology, Penn State Hershey College of Medicine, Hershey, PA, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Bhavi P
authors.initials: BP
authors.lastname: Modi
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
mesh_terms: D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
keywords: GWAS; PCOS; genomics; hyperandrogenism; signaling; theca