Study Report

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Basic Info

Reference	Papadimitriou, G. N., 1998 PMID: 9514592
Citation	Papadimitriou, G. N., D. G. Dikeos, et al. (1998). "Association between the GABA(A) receptor alpha5 subunit gene locus (GABRA5) and bipolar affective disorder." Am J Med Genet 81(1): 73-80.
Disease Type	Bipolar Disorder & Major Depressive Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	48 BP patients, 40 UP patients and 50 healthy individuals
SNP/Region/Marker Size	1 marker
Predominant Ethnicity	Caucasian
Population	Greek

Detail Info

Sample Diagnosis	DSM-IV and ICD-10
Sample Status	The majority of patients (n=81) were selected on a consecutive admissions basis from the outpatient and inpatient services of the Department of Psychiatry of Eginition University Hospital without prior knowledge of the presence or absence of psychopathology in the first-degree relatives. The remaining seven patients (all BP) were the probands of families collected for linkage studies of affective disorders. Among the BP patients, 41 were classified as having bipolar I disorder and seven as having bipolar II disorder. Out of the 40 UP patients, 34 suffered from recurrent major depression and the remaining from major depression, single episode.
Technique	genotyping
Statistical Method	The comparison of allelic and genotypic distribution among the groups of patients and controls was made by chi-square tests. As several statistical tests were performed, Bonferroni's correction was used to gauge statistical significance. Odds ratio and confidence limits were calculated by the Mantel-Haenszel procedure, controlling for gender. In order to further explore the relationship of BP disorder (as dependent) with the genotype, a multiple regression analysis was applied, controlling for potential confounding factors as gender, age, and family history.
Result Summary	The distribution of allelic frequencies of the GABRA5 locus differed significantly between BP patients and controls with the 282-bp allele found to be associated with BP affective disorder, while no such difference was observed between the groups of UP patients and controls nor between the two patient groups. The presence or absence of the 282-bp allele in the genotype of BP patients was not shown to influence the age of onset and the overall clinical severity, but was found to be associated with a preponderance of manic over depressive episodes in the course of the illness.

Genetic factors reported by this study for BD

Other variants reported by this study for BD (count: 1)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
GABRA5 (CA)n	GABRA5	polymorphic dinucleotide repeat marker			Overall P-value=0.043, X²=15.98, df=8; BP vs. Controls: X²=15.22, df=4,P-value=0.004; allelic P-value=0.007, X²=7.30 for 282bp; P-value=0.30, X²=0.88 for 284bp; P-value=0.10, X²=2.51 for 286bp; P-value=0.90, X²=0.01 for 288bp; P-value=0.002, X²=9.84, df=1 for distribution of genotypes with presence or absence of the 282-base pairs allele in BP patients; multiple linear regression of BD from genotype, P-value=0.008, t=2.705	In the analysis between pairs of groups, a statistically sig...... In the analysis between pairs of groups, a statistically significant difference was found between the BP patients and controls. The finding regarding the difference in the allelic frequencies between BP patients and controls remained significant (P<0.02) after the correction. The 282-bp allele was the only one found to be positively associated with BP affective disorder at a significant level. This significance persisted after the Bonferroni correction (P=0.028). Regarding the distribution of genotypes in BP patients and controls, a statistically significant association existed between the 282-bp allele containing genotypes and BP disorder. The multiple regression analysis also showed that the genotype containing the 282-bp allele was significantly associated with BP disorder (P 4 0.008). More...	Positive

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

Gene	Statistical Values/Author Comments	Result Category
GABRA5	The distribution of allelic frequencies of the GABRA5 locus differed significantly between BP patien...... The distribution of allelic frequencies of the GABRA5 locus differed significantly between BP patients and controls with the 282-bp allele found to be associated with BP affective disorder. More...	Positive

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

Other variants reported by this study for SZ/MDD

Disease	Variant Name	Related Gene	Type	Statistical Values	Description	Result Category
MDD	GABRA5 (CA)n	GABRA5	polymorphic dinucleotide repeat marker	Overall P-value=0.043, X²=15.98, df=8; UP vs. Controls: X²=2.92, df=4, P-value=NS	In the analysis between pairs of groups, a statistically significant difference was found between the BP patients and controls (P=0.004), while no such differences were observed between the groups of UP patients and controls.	Positive

Genes reported by this study for SZ/MDD

Disease	Gene	Description	Result Category
MDD	GABRA5	The distribution of allelic frequencies of the GABRA5 locus differed significantly between BP patients and controls with the 282-bp allele found to be associated with BP affective disorder, while no such difference was observed between the groups of UP patients and controls nor between the two patient groups.	Positive