Genome-wide association study identified new susceptibility loci for polycystic ovary syndrome

Hum Reprod. 2015 Mar;30(3):723-31. doi: 10.1093/humrep/deu352. Epub 2015 Jan 8.


Study question: Are there any novel genetic markers of susceptibility to polycystic ovary syndrome (PCOS)?

Summary answer: We identified a novel susceptibility locus on chromosome 8q24.2 and several moderately associated loci for PCOS in Korean women.

What is known already: 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.

Study design, size, duration: 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.

Participants/materials, setting, 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.

Main results and the role of chance: 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.

Limitations, reasons for caution: 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.

Wider implications of the findings: 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.

Study funding/competing interests: 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.

Keywords: genome-wide association study; polycystic ovary syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Chromosomes, Human, Pair 8
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Polycystic Ovary Syndrome / genetics*
  • Republic of Korea


  • Genetic Markers