title: Pathway Analysis Based on a Genome-Wide Association Study of Polycystic Ovary Syndrome.
abstract: BACKGROUND
  Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, and it is affected by both environmental and genetic factors. Although the genetic component of PCOS is evident, studies aiming to identify susceptibility genes have shown controversial results. This study conducted a pathway-based analysis using a dataset obtained through a genome-wide association study (GWAS) to elucidate the biological pathways that contribute to PCOS susceptibility and the associated genes.
  
  
  METHODS
  We used GWAS data on 636,797 autosomal single nucleotide polymorphisms (SNPs) from 1,221 individuals (432 PCOS patients and 789 controls) for analysis. A pathway analysis was conducted using meta-analysis gene-set enrichment of variant associations (MAGENTA). Top-ranking pathways or gene sets associated with PCOS were identified, and significant genes within the pathways were analyzed.
  
  
  RESULTS
  The pathway analysis of the GWAS dataset identified significant pathways related to oocyte meiosis and the regulation of insulin secretion by acetylcholine and free fatty acids (all nominal gene-set enrichment analysis (GSEA) P-values < 0.05). In addition, INS, GNAQ, STXBP1, PLCB3, PLCB2, SMC3 and PLCZ1 were significant genes observed within the biological pathways (all gene P-values < 0.05).
  
  
  CONCLUSIONS
  By applying MAGENTA pathway analysis to PCOS GWAS data, we identified significant pathways and candidate genes involved in PCOS. Our findings may provide new leads for understanding the mechanisms underlying the development of PCOS.
authors: Department of Internal Medicine, Seoul Seonam Hospital, Ewha Womans University Medical Center, Seoul, Korea.
authors: Unjin
authors: U
authors: Shim
authors: Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea.
authors: Han-Na
authors: HN
authors: Kim
authors: Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
authors: Hyejin
authors: H
authors: Lee
authors: Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
authors: Jee-Young
authors: JY
authors: Oh
authors: Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea.
authors: Yeon-Ah
authors: YA
authors: Sung
authors: Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea.
authors: Hyung-Lae
authors: HL
authors: Kim
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015201:Meta-Analysis as Topic; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D015415:Biomarkers