BDgene

Core Gene from Gene Prioritization Pathways from PBA (Pathway-based Analysis) Enriched Pathways for Core Genes Enriched Pathways for Cross-disorder Genes

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Study Report

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Basic Info

Reference	Duffy, A.,2000 PMID: 11022400
Citation	Duffy, A., G. Turecki, et al. (2000). "Association and linkage studies of candidate genes involved in GABAergic neurotransmission in lithium-responsive bipolar disorder." J Psychiatry Neurosci 25(4): 353-358.
Disease Type	Bipolar I Disorder
Study Design	pedigree and case-control
Study Type	Candidate-gene association study
Sample Size	138 bipolar patients and 108 controls foe association study;twenty-four probands for linkage study
SNP/Region/Marker Size	3 variants
Predominant Ethnicity	Caucasian
Population	Canadian,Czech and German
Gender	The sex ratio(M/F) was 0.87 for BD patients and 0.86 for controls
Age Group	Adults : Mean age(SD)(year):50.0(14.4) for BD patients and 51.5(14.8) for controls

Detail Info

Sample Diagnosis	RDC
Sample Status	The subjects for this study were 138 bipolar patients followed by the International Group for the Study of Lithium (IGSLI) in research clinics in Austria, Canada,Czech Republic, Denmark, Germany, and Sweden.In addition to a diagnosis of bipolar illness, all subjects met criteria for definite prophylactic response to lithium as described previously [Turecki et al., 1998]. The probands had a high recurrence risk as evidenced by a high number of illness episodes prior to lithium treatment (8.2 ,SD=10.1) and they had been fully stabilized on lithium monotherapy for 14.4 ,SD=6.8 years. To further ensure reliability of the diagnoses and uniform determination of the lithium response, all case histories and records have been reviewed by a single senior clinical investigator (PG) who also personally re-interviewed all subjects in Canada, Czech Republic, and Germany. The comparison group consisted of 108 psychiatrically healthy subjects. They were married-in family members in the linkage sample or healthy volunteers. Twenty-four probands had families available for a linkage study. A total of 171 subjects in these families were interviewed and genotyped, of these 72 were affected with a bipolar-spectrum disorder (bipolar I or bipolar II disorder, recurrent schizoaffective disorder, or recurrent unipolar depression). Six of the probands in the linkage study have been involved in a longitudinal investigation of the HPA axis using sequential dexamethasone suppression tests. They all showed intermittent positivity of the test while fully stabilized on lithium [Deshauer et al., 1999]. Families of these subjects were analyzed separately for linkage, as well as being included in the analysis of the entire sample.
Technique	PCR and electrophoresis
Statistical Method	Association data were analyzed by X² tests.The linkage data were analyzed by both nonparametric (GENEHUNTER and SimIBD) and parametric (FASTLINK) methods.
Result Summary	There was no significant association or linkage found between lithium-responsive bipolar disorder and the GABAergic candidate genes investigated. This study does not support a major role for the GABAergic candidate genes tested in lithium-responsive bipolar disorder.

Other variants reported by this study for BD (count: 3)

Variant Name	Related Gene	Type	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
GABRA3 GDB156286	GABRA3	VNTR	multi-allelic repeats		Association analysis:chi square tests, allele, chi square=4.03, P-value = 0.25;Linkage study:LOD under all models tested were negative for all theta<=0.1	Neither significant association nor significant linakge was ...... Neither significant association nor significant linakge was observed in BD. More...	Negative
GABRB3 GDB160763	GABRB3	VNTR	multi-allelic repeats		Association analysis:chi square tests, allele, chi square=5.29, P-value = 0.39;Linkage study:LOD under all models tested were negative for all theta<=0.1	Neither significant association nor significant linakge was ...... Neither significant association nor significant linakge was observed in BD. More...	Negative
GABRA5 GDB162554	GABRA5	VNTR	multi-allelic repeats		Association analysis:chi square tests, allele, chi square=21.64, P-value = 0.015;Linkage study:LOD under all models tested were negative for all theta<=0.1	Significant association was found in BPD patients. Significant association was found in BPD patients.	Positive

Genes reported by this study for BD (count: 3)

Gene	Statistical Values/Author Comments	Result Category
GABRA5	In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribut...... In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. More...	Positive
GABRB3	In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribut...... In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. More...	Negative
GABRA3	In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribut...... In conclusion, our study does not support the hypothesis that genes coding for CRH or PENK contribute to the genetic susceptibility to bipolar disorder. More...	Negative