Possible association between a haplotype of the GABA-A receptor alpha 1 subunit gene (GABRA1) and mood disorders
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Updated: Aug 29, 2026

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons
Published on: June 6, 2025
Yasue Horiuchi1, Junko Nakayama, Hiroki Ishiguro
1Department of Medical Genetics, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Background:
The gamma-aminobutyric acid (GABA) neurotransmitter system has been implicated in the pathogenesis of mood disorders. The GABRA1 gene encodes one of the subunits of GABA-A receptor and is located on human chromosome 5q34-q35, which is a region reportedly linked to mood disorders. We examined the GABRA1 gene as a candidate for mood disorders.
Methods:
We performed mutation screening of GABRA1 in 24 Japanese bipolar patients and evaluated associations in Japanese case-control subjects consisting of 125 patients with bipolar disorder, 147 patients with depressive disorders, and 191 healthy control subjects. Associations were confirmed in the National Institute of Mental Health (NIMH) Initiative Bipolar Pedigrees, which consists of 88 multiplex pedigrees with 480 informative persons.
Results:
We identified 13 polymorphisms in the GABRA1 gene. Nonsynonymous mutations were not found. Association of a specific haplotype with affective disorders was suggested in the Japanese case-control population (corrected p=.0008). This haplotype association was confirmed in the NIMH pedigrees (p=.007).
Conclusions:
These results indicate that the GABRA1 gene may play a role in the etiology of bipolar disorders.
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