title: TPH2 gene polymorphisms and bipolar disorder: A meta-analysis.
abstract: BACKGROUND
  Disturbance of the serotonergic system contributes to the etiology of bipolar disorder (BD). Tryptophan hydroxylase-2 (TPH2) is an important rate-limiting enzyme in the synthetic pathway for brain serotonin and has been suggested to play a role in BD.
  
  
  METHODS
  We performed a systematic review and meta-analysis of all studies to date investigating the association studies between TPH2 and BD published before Aug 2014. All studies were abstracted from PubMed, Embase, HuGNet, and China National Knowledge Infrastructure (CNKI). Manuscripts and the supplementary documents of published genome-wide association studies in the field were also included. Effect sizes of independent loci that have been studied in more than three articles were synthesized using fixed and random effects models.
  
  
  RESULTS
  Eight eligible studies addressed association between 63 TPH2 gene single nucleotide polymorphisms (SNPs) with BD, after linkage disequilibrium analysis, 12 independent SNPs were identified. Finally, three SNPs (rs4760820, rs11178998, and rs7954758) were found associated with BD using fixed effects models, and rs4760820 and rs11178998 were still associated with BD even with the more conservative random effects models.
  
  
  CONCLUSIONS
  rs4760820 and rs11178998 were identified to have strong genetic association with BD in present study though confirmation will require larger sample sizes and in additional populations.
authors.affiliation: Department of Clinical Psychology, Qilu Hospital of Shandong University, QingDao, Shandong, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pain, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Mingrui
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of psychology, Shandong Mental Health Center, Jinan, Shandong, China.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Qiao
authors.affiliation: Department of psychology, Shandong Mental Health Center, Jinan, Shandong, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Division of Immunology and Rheumatology, Stanford University Medial Center, and VA Palo Alto Health Care System, Palo Alto, California.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sokolove
authors.affiliation: Department of psychology, Shandong Mental Health Center, Jinan, Shandong, China.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Rheumatology, Qilu Hospital of Shandong University, QingDao, Shandong, China.
authors.forename: Zhenglun
authors.initials: Z
authors.lastname: Pan
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014365:Tryptophan Hydroxylase / Q000235:genetics*
chemical_list: C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase
keywords: association; bipolar; meta-analysis; tryptophan hydroxylase-2