title: Evidence for chromosome 2p16.3 polycystic ovary syndrome susceptibility locus in affected women of European ancestry.
abstract: BACKGROUND
  A previous genome-wide association study in Chinese women with polycystic ovary syndrome (PCOS) identified a region on chromosome 2p16.3 encoding the LH/choriogonadotropin receptor (LHCGR) and FSH receptor (FSHR) genes as a reproducible PCOS susceptibility locus.
  
  
  OBJECTIVE
  The objective of the study was to determine the role of the LHCGR and/or FSHR gene in the etiology of PCOS in women of European ancestry.
  
  
  METHODS
  This was a genetic association study in a European ancestry cohort of women with PCOS.
  
  
  METHODS
  The study was conducted at an academic medical center.
  
  
  METHODS
  Participants in the study included 905 women with PCOS diagnosed by National Institutes of Health criteria and 956 control women.
  
  
  METHODS
  We genotyped 94 haplotype-tagging single-nucleotide polymorphisms and two coding single-nucleotide polymorphisms mapping to the coding region of LHCGR and FSHR plus 20 kb upstream and downstream of the genes and test for association in the case control cohort and for association with nine quantitative traits in the women with PCOS.
  
  
  RESULTS
  We found strong evidence for an association of PCOS with rs7562215 (P = 0.0037) and rs10495960 (P = 0.0046). Although the marker with the strongest association in the Chinese PCOS genome-wide association study (rs13405728) was not informative in the European populations, we identified and genotyped three markers (rs35960650, rs2956355, and rs7562879) within 5 kb of rs13405728. Of these, rs7562879 was nominally associated with PCOS (P = 0.020). The strongest evidence for association mapping to FSHR was observed with rs1922476 (P = 0.0053). Furthermore, markers with the FSHR gene region were associated with FSH levels in women with PCOS.
  
  
  CONCLUSIONS
  Fine mapping of the chromosome 2p16.3 Chinese PCOS susceptibility locus in a European ancestry cohort provides evidence for association with two independent loci and PCOS. The gene products LHCGR and FSHR therefore are likely to be important in the etiology of PCOS, regardless of ethnicity.
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
authors.forename: Priscilla
authors.initials: P
authors.lastname: Mutharasan
authors.forename: Eugene
authors.initials: E
authors.lastname: Galdones
authors.forename: Beatriz
authors.initials: B
authors.lastname: Peñalver Bernabé
authors.forename: Obed A
authors.initials: OA
authors.lastname: Garcia
authors.forename: Nadereh
authors.initials: N
authors.lastname: Jafari
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
authors.forename: Teresa K
authors.initials: TK
authors.lastname: Woodruff
authors.forename: Richard S
authors.initials: RS
authors.lastname: Legro
authors.forename: Andrea
authors.initials: A
authors.lastname: Dunaif
authors.forename: Margrit
authors.initials: M
authors.lastname: Urbanek
mesh_terms: D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D011085:Polycystic Ovary Syndrome / Q000208:ethnology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011962:Receptors, FSH / Q000235:genetics; D011974:Receptors, LH / Q000235:genetics; D014481:United States; D044465:White People / Q000235:genetics*
chemical_list: D011962:Receptors, FSH; D011974:Receptors, LH