title: Genotype-phenotype correlations of PCOS susceptibility SNPs identified by GWAS in a large cohort of Han Chinese women.
abstract: OBJECTIVE
  Are there any correlations between the phenotypes of polycystic ovary syndrome (PCOS) and the genotypes of the PCOS susceptibility single nucleotide polymorphisms (SNPs) in THADA, DENND1A and LHCGR?
  
  
  CONCLUSIONS
  The PCOS susceptibility genes, THADA and DENND1A, carry risk alleles that are associated with endocrine and metabolic disturbances in patients with PCOS.
  
  
  BACKGROUND
  PCOS is a heterogeneous endocrinopathy characterized by oligo-anovulation, hyperandrogenism and polycystic ovaries. In a previous genome-wide association study, the SNP variants rs13429458, rs12478601, rs2479106, rs10818854 and rs13405728 in the THADA, DENND1A and LHCGR genes were identified as being independently associated with PCOS. The aim of this study was to identify any additional correlations between the phenotypes of PCOS and genotypes of the five SNPs described in the previous study.
  
  
  METHODS
  In the present cross-sectional study, a total of 1731 PCOS patients and 4964 controls were enrolled.
  
  
  METHODS
  Patients were diagnosed according to Rotterdam criteria. Clinical information was collected from the patients and controls. Endocrine and metabolic parameters were evaluated for phenotype-genotype correlation analyses.
  
  
  RESULTS
  Using a recessive model, the AA group for rs13429458 in THADA was associated with increased luteinizing hormone (LH) (P < 0.01) and testosterone (T) (P = 0.02) levels in subjects with PCOS; the LH/follicle-stimulating hormone ratio was also higher in the AA group (P < 0.01). Also using a recessive model, the CC genotype of rs12478601, also in THADA, was associated with increased levels of low-density lipoprotein (P = 0.02). Using a dominant model, the GG + AG group for rs2479106 in DENND1A was associated with elevated serum insulin levels 2 h after a glucose load in the patients with PCOS (P = 0.02). All of the comparisons were adjusted for age and BMI.
  
  
  CONCLUSIONS
  The relatively younger age of the participants may represent a considerable bias when evaluating metabolic alterations as a function of different genotypes, as significant metabolic disturbances may emerge later in life. Furthermore, the sample sizes of several sub-genotype groups were relatively small; to some extent this limited the statistical power of the analysis.
  
  
  CONCLUSIONS
  The PCOS susceptibility genes, THADA and DENND1A, carry risk alleles that are associated with endocrine and metabolic disturbances in PCOS patients of Han Chinese descent. The findings have shown genuine heterogeneity, stratified on the basis of both clinical findings and genotypes. Replication of these results is expected in other ethnic groups.
authors.affiliation: Center for Reproductive Medicine,  Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan 250021,  China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Cui
authors.forename: Han
authors.initials: H
authors.lastname: Zhao
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Qu
authors.forename: Jiayin
authors.initials: J
authors.lastname: Liu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liang
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhao
authors.forename: Junli
authors.initials: J
authors.lastname: Zhao
authors.forename: Yingpu
authors.initials: Y
authors.lastname: Sun
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Shi
authors.forename: Zi-Jiang
authors.initials: ZJ
authors.lastname: Chen
mesh_terms: D000328:Adult; D002681:China / Q000208:ethnology; D015331:Cohort Studies; D053418:Death Domain Receptor Signaling Adaptor Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011974:Receptors, LH / Q000235:genetics
chemical_list: C571984:DENND1A protein, human; D053418:Death Domain Receptor Signaling Adaptor Proteins; D020662:Guanine Nucleotide Exchange Factors; D009363:Neoplasm Proteins; D011974:Receptors, LH; C477698:THADA protein, human