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Gene Variant Linked to Risk of Bipolar Disorder

Case-control study finds deletion in GRIK4 gene associated with lower risk of disorder

THURSDAY, Oct. 2 (HealthDay News) -- A deletion variant in the glutamate receptor gene GRIK4 appears to offer protection against bipolar disorder, according to research published in the Sept. 30 issue of the Proceedings of the National Academy of Sciences.

Ben S. Pickard, Ph.D., of the University of Edinburgh in the United Kingdom, and colleagues previously demonstrated that two separated haplotypes within the gene were associated with increased risk of schizophrenia and decreased risk of bipolar disorder. In the new study, the investigators genotyped an indel variant in 356 subjects with the disorder and 286 healthy controls.

The researchers report that the deletion allele was present in more control individuals, resulting in an odds ratio of 0.4624. In a replication study in an independent cohort of cases and controls, the deletion allele was also found at a higher frequency in the controls compared to those with the disorder, resulting in an odds ratio of 0.6945.

"Single nucleotide polymorphisms in the GRIK4 and 5HTR2A genes have been linked to the responsiveness of depressed patients to citalopram, a serotonin reuptake inhibitor antidepressant. Whether these variants are related to the schizophrenia or bipolar variants that we have detailed or represent novel functional variation within the gene remains to be clarified. The GRIK4 findings presented here raise the possibility that pharmacologically mediated increases in kainate receptor activity, mirroring the protective deletion's effect on expression, might present a therapeutic opportunity for bipolar disorder and other psychiatric illnesses," the authors conclude.

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