Article

G72/G30 in Schizophrenia and Bipolar Disorder: Review and Meta-analysis

National Institute of Mental Health Intramural Research Program, National Institutes of Health, U.S. Department of Health and Human Services, Bethesda, Maryland 20892-3719, USA.
Biological Psychiatry (Impact Factor: 10.25). 08/2006; 60(2):106-14. DOI: 10.1016/j.biopsych.2006.01.019
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ABSTRACT Association of the G72/G30 locus with schizophrenia and bipolar disorder has now been reported in several studies. The G72/G30 locus may be one of several that account for the evidence of linkage that spans a broad region of chromosome 13q. However, the story of G72/G30 is complex. Our meta-analysis of published association studies shows highly significant evidence of association between nucleotide variations in the G72/G30 region and schizophrenia, along with compelling evidence of association with bipolar disorder. But the associated alleles and haplotypes are not identical across studies, and some strongly associated variants are located approximately 50 kb telomeric of G72. Interestingly, G72 and G30 are transcribed in opposite directions; hence, their transcripts could cross-regulate translation. A functional native protein and functional motifs for G72 or G30 remain to be demonstrated. The interaction of G72 with d-amino acid oxidase, itself of interest as a modulator of N-methyl-d-aspartate receptors through regulation of d-serine levels, has been reported in one study and could be a key functional link that deserves further investigation. The association findings in the G72/G30 region, among the most compelling in psychiatry, may expose an important molecular pathway involved in susceptibility to schizophrenia and bipolar disorder.

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Available from: Francis J Mcmahon, Aug 28, 2015
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    • "Interestingly, the NALCN gene lies within a region on chromosome 13q that has shown linkage to both BD and SCZ (reviewed in Detera-Wadleigh and McMahon, 2006). More specifically, the correlation between NALCN mRNA expression and the SCZ-associated gene GABRB2 in human brain (Kang et al., 2011), along with the association between the Drosophila homolog, na with circadian rhythms (disruptions of which are a hallmark of BD) suggest that NALCN may play a role in these two disorders (reviewed in Lenox et al., 2002). "
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    • "Nevertheless, lithium has been used for over 35 years for the treatment of BD, being the gold standard and perhaps the most widely used drug. Various theories on the mechanism of lithium action have been proposed, from alterations in ionic transport to modulation of gene expression [6] [7]. However, the precise neurobiological mechanisms through which lithium exerts its clinical effects are not clear, and some results found in the literature are contradictory [2]. "
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    • "Subsequently, numerous genetic association studies made the DAOA/G30 gene complex one of the most intriguing susceptibility loci for the major psychiatric disorders. The meta-analyses of published association studies supported weak, but significant genetic effects at the DAOA/G30 locus to schizophrenia for markers rs3916964 and rs2391191 or in Asian schizophrenia populations for rs947267 and rs778293, and in European populations for rs1421292 [4-6]. "
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