title: Replication of association of a novel insulin receptor gene polymorphism with polycystic ovary syndrome.
abstract: OBJECTIVE
  To evaluate association with polycystic ovary syndrome (PCOS) of 295 variants in 39 genes central to metabolic insulin signaling and glycogen synthase kinase 3β (GSK-3β) regulation, followed by replication efforts.
  
  
  METHODS
  Case-control association study, with discovery and replication cohorts.
  
  
  METHODS
  Subjects were recruited from reproductive endocrinology clinics, and controls were recruited from communities surrounding the University of Alabama at Birmingham and Erasmus Medical Center, Rotterdam.
  
  
  METHODS
  A total of 273 cases with PCOS and 173 control subjects in the discovery cohort; and 526 cases and 3,585 control subjects in the replication cohort. All subjects were caucasian.
  
  
  METHODS
  Phenotypic and genotypic assessment.
  
  
  METHODS
  Detection of 295 single-nucleotide polymorphisms (SNPs), PCOS status.
  
  
  RESULTS
  Several SNPs were associated with PCOS in the discovery cohort. Four insulin receptor (INSR) SNPs and three insulin receptor substrate 2 (IRS2) SNPs associated with PCOS were genotyped in the replication cohort. One INSR SNP (rs2252673) replicated association with PCOS. The minor allele conferred increased odds of PCOS in both cohorts, independent of body mass index.
  
  
  CONCLUSIONS
  A pathway-based tagging SNP approach allowed us to identify novel INSR SNPs associated with PCOS, one of which confirmed association in a large replication cohort.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. mark.goodarzi@cshs.org
authors.forename: Mark O
authors.initials: MO
authors.lastname: Goodarzi
authors.forename: Yvonne V
authors.initials: YV
authors.lastname: Louwers
authors.forename: Kent D
authors.initials: KD
authors.lastname: Taylor
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Jones
authors.forename: Jinrui
authors.initials: J
authors.lastname: Cui
authors.forename: Soonil
authors.initials: S
authors.lastname: Kwon
authors.forename: Yii-Der I
authors.initials: YD
authors.lastname: Chen
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Guo
authors.forename: Lisette
authors.initials: L
authors.lastname: Stolk
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Joop S E
authors.initials: JS
authors.lastname: Laven
authors.forename: Ricardo
authors.initials: R
authors.lastname: Azziz
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D008954:Models, Biological; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011972:Receptor, Insulin / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D011972:Receptor, Insulin