A convergent functional genomics approach identifies GRK3 as a candidate gene for bipolar disordr on 22q

A. B. Niculescu, R. L. Hauger, D. S. Segal, R. Kuczenski, T. Barrett, J. R. Kelsoe

Research output: Contribution to journalArticle

Abstract

We have previously reported evidence of genetic linkage of bipolar disorder to markers on 22q. In our genome survey of 20 families, the highest lod score was 3.8 at D22S278, though positive lod scores were obtained over 20 cM in that region. Such broad linkage peaks are characteristic of complex genetic traits and considerably confound efforts to fine map genes. We have addressed this problem using a convergent functional genomics approach to identify genes of likely pathophysiological significance. Rats were treated with amphetamine and saline as an animal model of mania and sacrificed 24 hours later. Prefrontal cortex and amygdala were dissected and RNA isolated for gene expression studies using the Affymetrix U34A GeneChip. Out of 8,000 genes examined, one of the genes with the largest change in expression was G protein receptor coupled kinase 3 (GRK3). GRK3 may mediate homologous desensitization of D1 receptors. It also maps very near a linkage peak (D22S419) in our family set and others. Preliminary western blot analyses of lymphoblastoid cell lines from bipolar subjects from families with evidence of linkage to 22q suggest a decrease in GRK3 expression. These data argue that GRK3 may be a susceptibility gene for bipolar disorder.

Original languageEnglish (US)
Number of pages1
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume96
Issue number4
StatePublished - Aug 7 2000
Externally publishedYes

ASJC Scopus subject areas

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

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