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Am J Med Genet B Neuropsychiatr Genet. 2016 Mar;171B(2):145-52. doi: 10.1002/ajmg.b.32381. Epub 2015 Sep 14.

TPH2 gene polymorphisms and bipolar disorder: A meta-analysis.

Author information

1
Department of Clinical Psychology, Qilu Hospital of Shandong University, QingDao, Shandong, China.
2
Department of Pain, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
3
Department of psychology, Shandong Mental Health Center, Jinan, Shandong, China.
4
Division of Immunology and Rheumatology, Stanford University Medial Center, and VA Palo Alto Health Care System, Palo Alto, California.
5
Department of Rheumatology, Qilu Hospital of Shandong University, QingDao, Shandong, China.

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.

MATERIALS AND 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.

KEYWORDS:

association; bipolar; meta-analysis; tryptophan hydroxylase-2

PMID:
26365518
DOI:
10.1002/ajmg.b.32381
[Indexed for MEDLINE]

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