title: Genome-wide association study identified new susceptibility loci for polycystic ovary syndrome.
abstract: OBJECTIVE
  Are there any novel genetic markers of susceptibility to polycystic ovary syndrome (PCOS)?
  
  
  CONCLUSIONS
  We identified a novel susceptibility locus on chromosome 8q24.2 and several moderately associated loci for PCOS in Korean women.
  
  
  BACKGROUND
  PCOS is a highly complex disorder with significant contributions from both genetic and environmental factors. Previous genome-wide association studies (GWAS) in the Han Chinese population identified several risk loci for PCOS. However, GWAS studies on PCOS remain very few. The aim of this study was to identify novel markers of susceptibility to PCOS through GWAS.
  
  
  METHODS
  A two-stage GWAS was conducted. The initial discovery set for GWAS consisted of 976 PCOS cases and 946 controls. The second stage (replication study) included 249 PCOS cases and 778 controls.
  
  
  METHODS
  Patients were diagnosed according to the Rotterdam criteria. Genomic DNAs were genotyped using the HumanOmni1-Quad v1 array. In the replication stage, the 21 most promising signals selected from the discovery stage were tested for their association with PCOS.
  
  
  RESULTS
  One novel locus with genome-wide significance and seven moderately associated loci for PCOS were identified. The strongest association was on chromosome 8q24.2 (rs10505648, OR = 0.52, P = 5.46 × 10(-8)), and other association signals were located at 4q35.2, 16p13.3, 4p12, 3q26.33, 9q21.32, 11p13 and 1p22 (P = 5.72 × 10(-6)-6.43 × 10(-5)). The strongest signal was located upstream of KHDRBS3, which is associated with telomerase activity, and could drive PCOS and related phenotypes.
  
  
  CONCLUSIONS
  The limitation of our study is the modest sample size used in the replication cohort. The limited sample size may contribute to a lack of statistical power to detect an association or show a trend in severity.
  
  
  CONCLUSIONS
  Our findings provide new insight into the genetics and biological pathways of PCOS and could contribute to the early diagnosis and prevention of metabolic and reproductive morbidities.
  
  
  BACKGROUND
  This work was supported in part by the grant from the Korea Centers for Disease Control and Prevention (2009-E00591-00). The work was also supported by the Ewha Global Top5 Grant 2013 of Ewha Womans University. None of the authors has any conflict of interest to declare.
authors.affiliation: Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Jee-Young
authors.initials: JY
authors.lastname: Oh
authors.affiliation: Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea yasung@ewha.ac.kr.
authors.forename: Yeon-Ah
authors.initials: YA
authors.lastname: Sung
authors.affiliation: Department of Obstetrics and Gynecology, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Hyewon
authors.initials: H
authors.lastname: Chung
authors.affiliation: Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea.
authors.forename: Hyung-Lae
authors.initials: HL
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, Hallym University, Gangwon-do, Korea.
authors.forename: Gwang Sub
authors.initials: GS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, Hallym University, Gangwon-do, Korea.
authors.forename: Yoon Shin
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Eulji University College of Medicine, Seoul, Korea.
authors.forename: Jin Taek
authors.initials: JT
authors.lastname: Kim
mesh_terms: D000328:Adult; D002898:Chromosomes, Human, Pair 8; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D056910:Republic of Korea
chemical_list: D005819:Genetic Markers
keywords: genome-wide association study; polycystic ovary syndrome