Study Report

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Basic Info

Reference	Horiuchi, Y.,2004 PMID: 14706423
Citation	Horiuchi, Y., J. Nakayama, et al. (2004). "Possible association between a haplotype of the GABA-A receptor alpha 1 subunit gene (GABRA1) and mood disorders." Biol Psychiatry 55(1): 40-45.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control and family-based
Study Type	Candidate-gene association study
Sample Size	125 unrelated patients with bipolar disorders, 147 patients with depressive disorders and 191 control subjects
SNP/Region/Marker Size	13 variants
Predominant Ethnicity
Population	Japanese and NIMH collections
Gender	patients with bipolar disorders (70 men, 55 women),patients with depressive disorders (recurrent major depression; 63 men, 84 women), and control subjects(104 men, 87 women).
Age Group	Adults : patients with bipolar disorders (mean age 50.5,SD=12.1 years),patients with depressive disorders (recurrent major depression; mean age 55.5,SD=14.1 years), and control subjects(mean age 53.6,SD=9.1 years).

Detail Info

Sample Diagnosis	DSM
Sample Status	All subjects examined in this study were recruited from a geographic area located in central Japan. All patients met DSM-IV criteria for mood disorders. The subjects, both outpatients and inpatients,were followed for at least 6 months from the time of diagnosis.Data on DSM Axis I and II comorbidities were not available.Control subjects had not been evaluated for psychiatric disorders by a psychiatrist.The National Institute of Mental Health (NIMH) Genetics Initiative Bipolar Pedigrees are a panel of 88 multiplex pedigrees that include 480 informative persons. Diagnosis and ascertainment methods are described in detail elsewhere (NIMH Genetics Initiative Bipolar Group 1997). In addition to bipolar I disorder,three hierarchical diagnoses were used in this study. Model I comprised affected individuals diagnosed with schizoaffective disorder, bipolar type (SA/BP), or bipolar I disorder (BPI).Affected individuals under model II included those diagnosed under model I as well as those with bipolar II disorder (BPII).Model III included all individuals classified as affected under model II as well as those with unipolar recurrent depression.
Technique	PCR and RFLP
Statistical Method	chi-square analysis.A family-based linkage and association analysis was conducted with TDTPHASE (Dudbridge et al 2000).
Result Summary	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.

Genetic factors reported by this study for BD

SNPs reported by this study for BD (count: 1)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs2279020	GABRA1			Association analysis: genotype P-value = 0.25, allele P-value = 0.29	No significant association was observed in BD. No significant association was observed in BD.	Negative

Other variants reported by this study for BD (count: 5)

Variant Name	Related Gene	Type	Allele Change	Statistical Values	Author Comments	Result Category
GABRA1 IVS2-712(GT)n	GABRA1	microsatellite	(GT)n	Association analysis:COCAPHASE P-value = 0.04;Global TDT p values for the IVS2-712(GT)n polymorphism are .047 in Model I, .09 in Model II, and .25 in Model III in NIMH pedigrees.	Significant association was found in BPD patients. Significant association was found in BPD patients.	Positive
rs1129647	GABRA1	point mutation		Association analysis:genotype P-value = 0.01, allele P-value = 0.01;TDT P-value = 0.07(Model I), 0.04(Model II), 0.04(Model III) in NIMH pedigrees.	Significant association was found in BD. Significant association was found in BD.	Positive
GABRA1 IVS9+76A/G	GABRA1	point mutation	A/G	Association analysis:genotype P-value = 0.47, allele P-value = 0.5	No significant association was observed in BD. No significant association was observed in BD.	Negative
GABRA1 -471T/C	GABRA1	point mutation	T/C	Association analysis:genotype P-value = 0.65, allele P-value = 0.67	No significant association was observed in BD. No significant association was observed in BD.	Negative
GABRA1 -181A/G	GABRA1	point mutation	A/G	Association analysis:genotype P-value = 0.99, allele P-value = 0.93	No significant association was observed in BD. No significant association was observed in BD.	Negative

Genes reported by this study for BD (count: 1)

Gene	Statistical Values/Author Comments	Result Category
GABRA1	These results indicate that the GABRA1 gene may play a role in the etiology of bipolar disorders. These results indicate that the GABRA1 gene may play a role in the etiology of bipolar disorders.	Positive

Genetic factors reported by this study for SZ and/or MDD

SNPs reported by this study for SZ/MDD

Disease	SNP	Related Gene(s)	Statistical Values	Description	Result Category
MDD	rs2279020	GABRA1	Association analysis:genotype P-value = 0.55, allele P-value = 0.58	No significant association was observed.	Negative

Other variants reported by this study for SZ/MDD

Disease	Variant Name	Related Gene	Type	Statistical Values	Description	Result Category
MDD	GABRA1 -181A/G	GABRA1	point mutation	Association analysis:genotype P-value = 0.53, allele P-value = 0.56	No significant association was observed in MDD.	Negative
MDD	GABRA1 -471T/C	GABRA1	point mutation	Association analysis:genotype P-value = 0.99, allele P-value = 0.93	No significant association was observed in MDD.	Negative
MDD	GABRA1 IVS9+76A/G	GABRA1	point mutation	Association analysis:genotype P-value = 0.3, allele P-value = 0.32	No significant association was observed in MDD.	Negative
MDD	rs1129647	GABRA1	point mutation	Association analysis:genotype P-value = 0.07, allele P-value = 0.08	No significant association was observed.	Negative
MDD	GABRA1 IVS2-712(GT)n	GABRA1	microsatellite	Association analysis:COCAPHASE P-value = 0.29	No significant association was observed in MDD.	Negative

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
MDD	GABRA1	No significant association was reported in this study.	Negative