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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Basic Info

Reference	Hartz, S. M.,2011 PMID: 21191315
Citation	Hartz, S. M., P. Lin, et al. (2011). "Genetic association of bipolar disorder with the beta(3) nicotinic receptor subunit gene." Psychiatr Genet 21(2): 77-84.
Disease Type	Bipolar Disorder
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	916 European Americans (EA) with bipolar disorder and 1028 EA controls
SNP/Region/Marker Size	14 SNPs
Predominant Ethnicity
Population	European American and African American
Gender	males:359 for all BD patients(149 in non smokers,68 in smokers without nicotine dependence,142 in nicotine dependent smokers);599 for all controls(267 in non smokers,150 in smokers without nicotine dependence,182 in nicotine dependent smokers)
Age Group	Adults : Mean age(SD)(year):43.5(13.2) for all BD patients(42.7(13.5) in non smokers,43.9(13.4) in smokers without nicotine dependence,44.4(12.7) in nicotine dependent smokers);52.9(17.7) for all controls(48.7(17.4) in non smokers,57.6(18.1) in smokers without nicotine dependence,56.7(15.9) in nicotine dependent smokers)

Detail Info

Sample Diagnosis	DSM
Sample Status	All bipolar patients were recruited at 11 data collection sites as the fifth wave of data collection by the Bipolar Consortium.Control participants were collected separately through a volunteer panel and web-based psychiatric interview (Sanders et al., 2008). The replication sample (both the EA sample and AA sample) was collected and genotyped as part of the Genetic Association Information Network initiative. These data and corresponding documentation are available at dbGaP (http://www.ncbi.nlm.nih.gov/dbgap). The specific population and study characteristics are described in detail elsewhere (Dick et al., 2003; Smith et al., 2009, in preparation). Smoking covariates were collected in all participants.The participants with bipolar disorder had a higher proportion of smoking (58% of participants with bipolar disorder versus 51% of participants without bipolar disorder) and nicotine dependence (69% of smokers with bipolar disorder are nicotine dependent versus 52% of smokers without bipolar disorder).
Replication Size	595 EA patients with bipolar disorder and 394 EA controls, and 389 African American (AA) participants with bipolar disorder and 671 AA controls
Technique	genotyping
Statistical Method	To evaluate whether genetic associations for nicotine dependence are different in bipolar disorder as compared with the general population, a X² test was used to compare allele frequencies between participants with nicotine dependence and bipolar disorder and participants with nicotine dependence, but no bipolar disorder.To evaluate the association between SNPs and bipolar disorder in the primary data, we used a logistic regression model correcting for sex, age, and a population stratification principal component.
Result Summary	RESULTS: To determine whether the genetic associations with nicotine dependence are different in bipolar disorder than in the general population, we compared allele frequencies of candidate SNPs between individuals with nicotine dependence only and individuals with both nicotine dependence and bipolar disorder. There were no statistical differences between these frequencies, indicating that genetic association with nicotine dependence is similar in individuals with bipolar disorder as in the general population. In the investigation of pleiotropic effects of these SNPs on bipolar disorder, two highly correlated synonymous SNPs in CHRNB3, rs4952 and rs4953, were significantly associated with bipolar disorder (odds ratio 1.7, 95% confidence interval: 1.2-2.4, P=0.001). This association remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. CONCLUSION: Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder.

SNPs reported by this study for BD (count: 14)

SNP	Related Gene(s)	Allele Change	Risk Allele	Statistical Values	Author Comments	Result Category
rs16969968	CHRNA3 CHRNA5			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.97; logistic regression: for BD case-control, P-value = 0.36, OR=0.93, 95% CI=0.8-1.1, when smoking as a covariate, P-value = 0.36, OR=0.93, for non-smokers only, P-value = 0.21, OR=0.87	No significant association was observed. No significant association was observed.	Negative
rs1955185	CHRNB3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.28; logistic regression: for BD case-control, P-value = 0.09, OR=1.15, 95% CI=1.0-1.3, when smoking as a covariate, P-value = 0.06, OR=1.17, for non-smokers only, P-value = 0.38, OR=1.1	No significant association was observed. No significant association was observed.	Negative
rs3743078	CHRNA3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.13; logistic regression: for BD case-control, P-value = 0.37, OR=0.94, 95% CI=0.8-1.1, when smoking as a covariate, P-value = 0.3, OR=0.92, for non-smokers only, P-value = 0.74, OR=0.96	No significant association was observed. No significant association was observed.	Negative
rs4952	CHRNB3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.2; logistic regression: for BD case-control, P-value = 0.0011, OR=1.72, 95% CI=1.2-2.4, when smoking as a covariate, P-value = 0.0015, OR=1.71, for non-smokers only, P-value = 0.0025, OR=2.08	Significant association was found in bipolar disorder, and i...... Significant association was found in bipolar disorder, and it remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. More...	Positive
rs1051730	CHRNA3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.99; logistic regression: for BD case-control, P-value = 0.27, OR=0.92, 95% CI=0.8-1.1, when smoking as a covariate, P-value = 0.37, OR=0.93, for non-smokers only, P-value = 0.21, OR=0.87	No significant association was observed. No significant association was observed.	Negative
rs13277254	CHRNB3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.28; logistic regression: for BD case-control, P-value = 0.09, OR=1.15, 95% CI=1.0-1.3, when smoking as a covariate, P-value = 0.06, OR=1.16, for non-smokers only, P-value = 0.4, OR=1.1	No significant association was observed. No significant association was observed.	Negative
rs13277524	CHRNB3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.28; logistic regression: for BD case-control, P-value = 0.09, OR=1.15, 95% CI=1.0-1.3, when smoking as a covariate, P-value = 0.06, OR=1.17, for non-smokers only, P-value = 0.38, OR=1.1	No significant association was observed. No significant association was observed.	Negative
rs1530847	CHRNB3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.77; logistic regression: for BD case-control, P-value = 0.98, OR=1, 95% CI=0.8-1.2, when smoking as a covariate, P-value = 0.76, OR=1.03, for non-smokers only, P-value = 0.68, OR=0.95	No significant association was observed. No significant association was observed.	Negative
rs684513	CHRNA5			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.36; logistic regression: for BD case-control, P-value = 0.19, OR=0.9, 95% CI=0.8-1.1, when smoking as a covariate, P-value = 0.22, OR=0.9, for non-smokers only, P-value = 0.43, OR=0.91	No significant association was observed. No significant association was observed.	Negative
rs6474413	CHRNB3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.67; logistic regression: for BD case-control, P-value = 0.09, OR=1.15, 95% CI=1.0-1.3, when smoking as a covariate, P-value = 0.06, OR=1.16, for non-smokers only, P-value = 0.38, OR=1.1	No significant association was observed. No significant association was observed.	Negative
rs578776	CHRNA3 CHRNA5			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.41; logistic regression: for BD case-control, P-value = 0.3, OR=0.92, 95% CI=0.8-1.1, when smoking as a covariate, P-value = 0.28, OR=0.92, for non-smokers only, P-value = 0.37, OR=0.91	No significant association was observed. No significant association was observed.	Negative
rs4953	CHRNB3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.2; logistic regression: for BD case-control, P-value = 0.0008, OR=1.74, 95% CI=1.3-2.4, when smoking as a covariate, P-value = 0.0011, OR=1.74, for non-smokers only, P-value = 0.0017, OR=2.13	Significant association was found in bipolar disorder, and i...... Significant association was found in bipolar disorder, and it remained significant both after adjusting for a smoking covariate and analyzing the association in nonsmokers only. More...	Positive
rs6474412	CHRNB3			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.28; logistic regression: for BD case-control, P-value = 0.11, OR=1.14, 95% CI=1.0-1.3, when smoking as a covariate, P-value = 0.08, OR=1.15, for non-smokers only, P-value = 0.3, OR=1.12	No significant association was observed. No significant association was observed.	Negative
rs637137	CHRNA5			X² test: for nicotine dependence with and without bipolar disorder, allele P-value = 0.19; logistic regression: for BD case-control, P-value = 0.11, OR=0.88, 95% CI=0.7-1.0, when smoking as a covariate, P-value = 0.13, OR=0.88, for non-smokers only, P-value = 0.43, OR=0.91	No significant association was observed. No significant association was observed.	Negative

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

Gene	Statistical Values/Author Comments	Result Category
CHRNA5	No significant associations were detected in BD patients. No significant associations were detected in BD patients.	Negative
CHRNA3	No significant associations were detected in BD patients. No significant associations were detected in BD patients.	Negative
CHRNB3	Our results suggest that (i) bipolar disorder does not modify the association between nicotine depen...... Our results suggest that (i) bipolar disorder does not modify the association between nicotine dependence and nicotinic receptor subunit genes, and (ii) variants in CHRNB3/CHRNA6 are independently associated with bipolar disorder. More...	Positive