Polycystic Ovary Syndrome (PCOS) Genetics

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.

• Study Weblinks:
  • PCOS
  • NUgene
• Study Design:
  • Case-Control
• Study Type:
  • Case-Control
• dbGaP estimated ancestry using GRAF-pop
• Total number of consented subjects: 4151
• Subject Sample Telemetry Report (SSTR)

• PubMed

Study population
Suitable participant DNA samples from females self-identified as Caucasian or European-ancestry were selected from PCOS clinical study participants (cases), and from the NUgene biobank (controls).

Identification of Cases
Patients must have met all of the following criteria:

1. Females enrolled in one of the four participating PCOS studies
2. Fulfill the NICHD criteria for the diagnosis of PCOS:
1. elevated total testosterone (T) or biologically available T (uT) level
2. chronic anovulation defined by <8 menses/year;
3. exclusion of specific disorders of the pituitary, ovary or adrenal.

Identification of Controls
Patients must have met all of the following criteria:

1. Females enrolled in NUgene
2. self-reported Caucasian but no self-reported African ancestry and no self-reported Hispanic/Latino ancestry

Time Line

• 2010 - Samples shipped and received at CIDR
• 2011 - Genotyping of samples complete
• 2011 - Genotyping QC complete

• Primary Phenotype: Polycystic Ovary Syndrome

• Principal Investigator
  • Andrea Dunaif, MD. Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
• Institute
  • National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD, USA.
• Funding Source
  • R01HD057223. National Institutes of Health, Bethesda, MD, USA.