BDgene

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

Search Gene with Disease Search Gene1 with Disease

Study Report

Comment on Study

View All Comments on Study

Basic Info

Reference	Craddock, N., 2010 PMID: 19078961
Citation	Craddock, N., L. Jones, et al. (2010). "Strong genetic evidence for a selective influence of GABAA receptors on a component of the bipolar disorder phenotype." Mol Psychiatry 15(2): 146-153.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	total 2938 controls and 1868 BD cases, in which 279 RDC SABP cases.
SNP/Region/Marker Size	223 SNPs from WTCCC data set satisfying (1) had excellent genotyping quality, and (2) tagged common genetic variation at or near genesencoding GABAA receptors.
Predominant Ethnicity	Caucasian
Population	white and resident in the UK
Gender	42% men for the subste of 279 cases of RDC SABP.
Age Group	adult : 43.3 (s.d. 12.1) years for the subste of 279 cases of RDC SABP.

Detail Info

Sample Diagnosis	Research Diagnostic Criteria
Sample Status	The cases are from the BD component of the WTCCC genome-wide association study of seven common familial diseases. 11 phenotype subsets of BD were examined, including BD rapid cycling, RDC BPII, DSMIV BPII, DSMIV SABP, Psychosis with predominant mood incongruence, RDC BPI or manic disorder, DSMIV BPI, Lifetime psychosis, Psychosis in X50% of episodes, Age onset < 20 years, RDC SABP.
Technique	genotyping
Statistical Method	The Armitage trend test was used to assess association at each SNP in PLINK version 0.99. Forward step-wise logistic regression as implemented in SPSS version 12.0.1 were used for testing for additional evidence of association at genes while allowing for the specific association signals. Set-based analysis option within PLINK were used for testing for gene-wide significance for SNP association at genes. Canonical correlation analysis as implemented in SAS 8.02 (PROC CANCOR) were used to attempt to further refine the genotype-phenotype relationship within the RDC SABP sample (N= 279).
Result Summary	The index signal rs7680321 was significantly enriched in the 279 cases meeting Research Diagnostic Criteria for schizoaffective disorder, bipolar type (P= 3.8E-6). Independently, these cases showed strong evidence that variation in GABA_A receptor genes influences risk for this phenotype (independent system-wide P = 6.6E-5) with association signals also at GABRA4, GABRB3, GABRA5 and GABRR1.

SNPs reported by this study for BD (count: 5)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs17561681	GABRB3 GABRA5			Nominal P-value = 0.00016	showed significant levels independent of the association at ...... showed significant levels independent of the association at the index SNP, rs7680321. More...	Positive
rs7680321	GABRB1			OR= 1.80 (1.37-2.37), X² = 21.34, 1 d.f., P = 3.8E-6 in the subset of 279 bipolar cases that met Research Diagnostic Criteria (RDC SABP).	The index SNP, rs7680321 showed the strongest evidence for a...... The index SNP, rs7680321 showed the strongest evidence for association in the subset of SABP samples and substantially less strong in the subset of cases meeting criteria for DSMIV SABP or the larger subset of cases with predominantly moodincongruent psychotic features. More...	Positive
rs3934674	GABRB1 GABRA4			Nominal P-value = 6.87E-6	showed significant levels independent of the association at ...... showed significant levels independent of the association at the index SNP, rs7680321. More...	Positive
rs890319	GABRB3			Nominal P-value = 0.00046	showed significant levels independent of the association at ...... showed significant levels independent of the association at the index SNP, rs7680321. More...	Positive
rs854579	GABRR3			Nominal P-value = 0.0044	showed significant levels independent of the association at ...... showed significant levels independent of the association at the index SNP, rs7680321. More...	Positive

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
rs6414684	GABRB1	point mutation			Nominal P-value = 1.23E-6	showed significant levels independent of the association at ...... showed significant levels independent of the association at the index SNP, rs7680321. More...	Positive

Genes reported by this study for BD (count: 5)

Gene	Statistical Values/Author Comments	Result Category
GABRB1	logistic regression for gene-wide P-value = 0.0039. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples.	Positive
GABRB3	set-based analysis for gene-wide P-value = 0.0107. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples.	Positive
GABRA4	logistic regression for gene-wide P-value = 0.013. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples.	Positive
GABRR3	set-based analysis for gene-wide P-value = 0.044. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples.	Positive
GABRA5	set-based analysis for gene-wide P-value = 0.0024. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples. gene-wide levels of statistical significance in RDC SABP samples, but not other subsets of samples.	Positive