The purpose of this study was to identify biological pathways that contribute to risk for bipolar disorder using genes with consistent evidence for association in multiple genome-wide association studies (GWAS).
The authors identified 966 genes that contained 2 or more variants associated with Bipolar Disorder at P < .05 in 3 of 4 GWAS data sets. Seventeen pathways were overrepresented in analyses of the initial data set. Six of the 17 pathways were associated with Bipolar Disorder in both the initial and replication samples: corticotropin-releasing hormone signaling, cardiac β-adrenergic signaling, phospholipase C signaling, glutamate receptor signaling, endothelin 1 signaling, and cardiac hypertrophy signaling.
The study concluded that pathways involved in the genetic predisposition to Bipolar Disorder include hormonal regulation, calcium channels, second messenger systems, and glutamate signaling. Gene expression studies implicated neuronal development pathways as well. These results may provide clues for new approaches to treatment and prevention.

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Nurnberger JI Jr, Koller DL, Jung J, Edenberg HJ, Foroud T, Guella I, Vawter MP, Kelsoe JR: Psychiatric Genomics Consortium Bipolar Group. Identification of pathways for bipolar disorder: a meta-analysis. JAMA Psychiatry 71(6): 657-664 (2014).
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http://www.ncbi.nlm.nih.gov/pubmed/24718920

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