title: Disparate genetic influences on polycystic ovary syndrome (PCOS) and type 2 diabetes revealed by a lack of association between common variants within the TCF7L2 gene and PCOS.
abstract: OBJECTIVE
  Common variants of the gene encoding transcription factor 7-like 2 (TCF7L2) have a powerful effect on individual risk of type 2 diabetes (per allele odds ratio approximately 1.35). Polycystic ovary syndrome (PCOS) and type 2 diabetes are familial conditions sharing common features. Based on this, the aim of the present study was to establish whether variation in TCF7L2 also influences the development of PCOS.
  
  
  METHODS
  We conducted a genetic association study of variants of TCF7L2 (rs7903146 and rs12255372) using both case-control and quantitative trait approaches. Case-control analyses were conducted in (1) 369 PCOS cases and 2574 controls of UK British/Irish origin, and (2) 540 women with PCOS symptoms and 1083 controls from the Northern Finland Birth Cohort of 1966. Quantitative trait analyses (androgen levels) were also performed (1249 individuals).
  
  
  RESULTS
  There was no association between rs7903146 and PCOS in the UK case-control study (Cochran-Armitage test, p = 0.51); nor with symptomatic status in the Finnish cohort (p = 0.36). In addition, there were no relationships between the TCF7L2 single nucleotide polymorphism rs7903146 and androgen levels (UK cases, p = 0.99; Finnish controls, p = 0.57; Finnish symptomatic cases, p = 0.80). Results at rs12255372 were similar, reflecting strong linkage disequilibrium with rs7903146.
  
  
  CONCLUSIONS
  Our study was powered to detect an effect on PCOS susceptibility similar to that previously reported for these variants on type 2 diabetes. Failure to detect any evident association with PCOS provides the strongest evidence yet that the genetic architecture of these related conditions is qualitatively distinct.
authors.affiliation: Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, UK. tom.barber@drl.ox.ac.uk
authors.forename: T M
authors.initials: TM
authors.lastname: Barber
authors.forename: A J
authors.initials: AJ
authors.lastname: Bennett
authors.forename: C J
authors.initials: CJ
authors.lastname: Groves
authors.forename: U
authors.initials: U
authors.lastname: Sovio
authors.forename: A
authors.initials: A
authors.lastname: Ruokonen
authors.forename: H
authors.initials: H
authors.lastname: Martikainen
authors.forename: A
authors.initials: A
authors.lastname: Pouta
authors.forename: A-L
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: P
authors.initials: P
authors.lastname: Elliott
authors.forename: J A H
authors.initials: JA
authors.lastname: Wass
authors.forename: M-R
authors.initials: MR
authors.lastname: Järvelin
authors.forename: E
authors.initials: E
authors.lastname: Zeggini
authors.forename: S
authors.initials: S
authors.lastname: Franks
authors.forename: M I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051820:TCF Transcription Factors / Q000235:genetics*; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000235:genetics*