title: Polycystic ovary syndrome is not associated with genetic variants that mark risk of type 2 diabetes.
abstract: Polycystic ovary syndrome (PCOS) is a disorder of irregular menses, hyperandrogenism and/or polycystic ovary morphology. A large proportion of women with PCOS also exhibit insulin resistance, β-cell dysfunction, impaired glucose tolerance and/or type 2 diabetes (T2D). We therefore hypothesized that genetic variants that predispose to risk of T2D also result in risk of PCOS. Variants robustly associated with T2D in candidate gene or genome-wide association studies (GWAS; n = 56 SNPs from 33 loci) were genotyped in women of European ancestry with PCOS (n = 525) and controls (n = 472), aged 18-45 years. Metabolic, reproductive and anthropomorphic data were examined as a function of the T2D variants. All genetic association analyses were adjusted for age, BMI and ancestry and were reported after correction for multiple testing. There was a nominal association between variants in KCNJ11 and risk of PCOS. However, a risk score of 33 independent T2D-associated variants from GWAS was not significantly associated with PCOS. T2D variants were associated with PCOS phenotype parameters including those in THADA and WFS1 with testosterone levels, ENPP/PC1 with triglyceride levels, FTO with glucose levels and KCNJ11 with FSH levels. Diabetes risk variants are not important risk variants for PCOS.
authors.affiliation: Department of Anaesthesia, Massachusetts General Hospital, Boston, MA 02114, USA.
authors.forename: R
authors.initials: R
authors.lastname: Saxena
authors.forename: C K
authors.initials: CK
authors.lastname: Welt
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000097:blood; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D017588:Hyperandrogenism / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics; D010727:Phosphoric Diester Hydrolases / Q000235:genetics; D011085:Polycystic Ovary Syndrome / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011755:Pyrophosphatases / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics; D012307:Risk Factors; D013739:Testosterone / Q000097:blood; D014280:Triglycerides / Q000097:blood; D055815:Young Adult; D000099161:Kcnj11 Channel
chemical_list: D043373:Follicle Stimulating Hormone, Human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010727:Phosphoric Diester Hydrolases; D024661:Potassium Channels, Inwardly Rectifying; D011755:Pyrophosphatases; D013739:Testosterone; D014280:Triglycerides; D000099161:Kcnj11 Channel; C477698:THADA protein, human; C114987:wolframin protein; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1