Meta-analysis of genetic association studies on bipolar disorder

Fayaz Seifuddin, Pamela Belmonte Mahon, Jennifer Judy, Mehdi Pirooznia, Dubravka Jancic, Jacob Taylor, Fernando S. Goes, James B. Potash, Peter P. Zandi

Research output: Contribution to journalArticlepeer-review

Abstract

Numerous candidate gene association studies of bipolar disorder (BP) have been carried out, but the results have been inconsistent. Individual studies are typically underpowered to detect associations with genes of small effect sizes. We conducted a meta-analysis of published candidate gene studies to evaluate the cumulative evidence. We systematically searched for all published candidate gene association studies of BP. We then carried out a random-effects meta-analysis on all polymorphisms that were reported on by three or more case-control studies. The results from meta-analyses of these genes were compared with the findings from a recent mega-analysis of eleven genome-wide association studies (GWAS) in BP performed by the Psychiatric GWAS Consortium (PGC). A total of 487 articles were included in our review. Among these, 33 polymorphisms in 18 genes were reported on by three or more case-control studies and included in the random-effects meta-analysis. Polymorphisms in BDNF, DRD4, DAOA, and TPH1, were found to be nominally significant with a P-value<0.05. However, none of the findings were significant after correction for multiple testing. Moreover, none of these polymorphisms were nominally significant in the PGC-BP GWAS. A number of plausible candidate genes have been previously associated with BP. However, the lack of robust findings in our review of these candidate genes highlights the need for more atheoretical approaches to study the genetics of BP afforded by GWAS. The results of this meta-analysis and from other on-going genomic experiments in BP are available online at Metamoodics.

Original languageEnglish (US)
Pages (from-to)508-518
Number of pages11
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume159 B
Issue number5
DOIs
StatePublished - Jul 2012

Keywords

  • Candidate genes
  • Meta-analysis
  • Mood disorders

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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