title: Metabolic and cardiovascular genes in polycystic ovary syndrome: a candidate-wide association study (CWAS).
abstract: The role of metabolic disturbance in polycystic ovary syndrome (PCOS) has been well established, with insulin resistance and the resulting compensatory hyperinsulinemia thought to promote hyperandrogenemia. Genome-wide association studies (GWAS) have established a large number of loci for metabolic conditions such as type 2 diabetes and obesity. A subset of these loci has been investigated for a role in PCOS; these studies generally have not revealed a confirmed role for these loci in PCOS risk. However, a large scale investigation of genes related to these pathways has not previously been performed. We conducted a two stage case control association study of 121,715 single nucleotide polymorphisms (SNPs) selected to represent susceptibility loci associated with traits such as type 2 diabetes, obesity measures, lipid levels and cardiovascular function using the Cardio-Metabochip in 847 PCOS cases and 845 controls. Several hypothesis-generating associations with PCOS were observed (top SNP rs2129107, P=3.8×10(-6)). We did not find any loci definitively associated with PCOS after strict correction for multiple testing, suggesting that cardio-metabolic loci are not major risk factors underlying the susceptibility to PCOS.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States. michelle.jones@cshs.org
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Jones
authors.forename: Angela K
authors.initials: AK
authors.lastname: Chua
authors.forename: Emebet A
authors.initials: EA
authors.lastname: Mengesha
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.forename: Ricardo
authors.initials: R
authors.lastname: Azziz
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
mesh_terms: D000328:Adult; D001827:Body Height / Q000235:genetics; D002319:Cardiovascular System / Q000378:metabolism* / Q000503:physiopathology; D015331:Cohort Studies; D048909:Diabetes Complications / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D007958:Leukocyte Count; D050356:Lipid Metabolism / Q000235:genetics; D008875:Middle Aged; D010976:Platelet Count; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics