BACKGROUND: Schizophrenia is a severe neuropsychiatric disorder where the role of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter, has been implicated in its aetiopathophysiology. Several genes coding for GABAA subunits, including the GABRG2 gene that encodes the γ2 subunit, are clustered at 5q31-q35, a chromosomal region that is associated with schizophrenia in genome scan studies. We recently reported GABRG2 to be associated with schizophrenia in our case-control and family samples. METHODS: We tested eight single-nucleotide polymorphisms spanning the GABRG2 gene for an association with suicidal behaviour in our schizophrenia sample of European ancestry (n = 197), taking into account history of alcohol abuse or dependence. RESULTS: We found the haplotypes of the rs183294 and rs209356 markers to be significantly associated with history of suicide attempt (p < 0.01) as well as suicide specifier scores (p < 0.05). The association appeared to be originating in patients with a history of alcohol dependence or abuse. CONCLUSIONS: Taken together, the results of the present study suggest that GABRG2 may be involved in suicidal behaviour in schizophrenia patients with alcohol dependence or abuse, but replications are required. These results may help in the discovery of novel treatments for alcoholism and/or prevention of suicide.
Association study of GABRG2 polymorphisms with suicidal behaviour in schizophrenia patients with alcohol use disorder
MANCHIA, MIRKO;
2014-01-01
Abstract
BACKGROUND: Schizophrenia is a severe neuropsychiatric disorder where the role of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter, has been implicated in its aetiopathophysiology. Several genes coding for GABAA subunits, including the GABRG2 gene that encodes the γ2 subunit, are clustered at 5q31-q35, a chromosomal region that is associated with schizophrenia in genome scan studies. We recently reported GABRG2 to be associated with schizophrenia in our case-control and family samples. METHODS: We tested eight single-nucleotide polymorphisms spanning the GABRG2 gene for an association with suicidal behaviour in our schizophrenia sample of European ancestry (n = 197), taking into account history of alcohol abuse or dependence. RESULTS: We found the haplotypes of the rs183294 and rs209356 markers to be significantly associated with history of suicide attempt (p < 0.01) as well as suicide specifier scores (p < 0.05). The association appeared to be originating in patients with a history of alcohol dependence or abuse. CONCLUSIONS: Taken together, the results of the present study suggest that GABRG2 may be involved in suicidal behaviour in schizophrenia patients with alcohol dependence or abuse, but replications are required. These results may help in the discovery of novel treatments for alcoholism and/or prevention of suicide.
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