PCOS is a complex genetic disease reflecting the interplay of susceptibility genes and environmental factors. The cardinal reproductive feature of the syndrome, hyperandrogenemia, appears to play a direct role in the pathogenesis of the associated metabolic abnormalities. Male as well as female first-degree relatives have reproductive and metabolic phenotypes including increased prevalence rates of type 2 diabetes (T2D), metabolic syndrome (MBS) and other risk factors for cardiovascular disease (CVD). Northwestern University (NU) investigators lead a team that has extensive experience in phenotyping PCOS and in the genetic analysis of complex diseases including genome-wide association study (GWAS). Together with an expert group of collaborators from the Hershey Medical Center, and The University of Chicago, we have conducted a GWAS to identify PCOS susceptibility alleles using a large cohort of extensively and consistently phenotyped PCOS cases. Population controls for this study come from the NUgene project described below. NUgene project: In 2002, Northwestern committed to the development of a DNA repository to serve as a platform for the identification and validation of genotype-phenotype associations that will impact healthcare. The NUgene Project is a repository with longitudinal medical information from participating patients at affiliated hospitals and outpatient clinics from the Northwestern University Medical Center. Participants' DNA samples are coupled with data from a questionnaire (2 versions were used, 1 before and 1 after February 2006, both are included) and continuously updated data from our Electronic Medical Record (EMR) representing actual clinical care events. Northwestern has a state-of-the art, comprehensive inpatient and outpatient EMR system of over 2 million patients. NUgene has broad access to participant data for all outpatient visits as well as inpatient data via a consolidated data warehouse. NUgene participants consent to distribution and use of their coded DNA samples and data for a broad range of genetic research by third-party investigators.

POLYGEN

The genetics of the polycystic ovary syndrome

Identification of a polycystic ovary syndrome susceptibility variant in fibrillin-3 and association with a metabolic phenotype.

The role of genetic variation in the lamin a/c gene in the etiology of polycystic ovary syndrome.

Evidence for association between polycystic ovary syndrome (PCOS) and TCF7L2 and glucose intolerance in women with PCOS and TCF7L2.

Variation in the perilipin gene (PLIN) affects glucose and lipid metabolism in non-Hispanic white women with and without polycystic ovary syndrome.