Year: 2010
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Owing to the clinical relationship between bipolar disorder and nicotine dependence, we investigated two research questions: (i) are genetic associations with nicotine dependence different in individuals with bipolar disorder as compared with individuals without bipolar disorder, and (ii) do loci earlier associated with nicotine dependence have pleiotropic effects on these two diseases. METHOD: Our study consisted of 916 cases with bipolar disorder and 1028 controls. On the basis of known associations with nicotine dependence, we genotyped eight single-nucleotide polymorphisms (SNPs) on chromosome 8 (three bins) in the regions of CHRNB3 and CHRNA6, and six SNPs on chromosome 15 (three bins) in the regions of CHRNA5 and CHRNA3. 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.
Source: Psychiatric Genetics
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Wayne State University, University of Pennsylvania, Johns Hopkins University, University of Louisville, Rush University, Virginia Commonwealth University, University of Oxford, Ministry of Education, India, National Institutes of Health, National Institute of Mental Health, National Institute on Drug Abuse, National Cancer Institute, National Center for Advancing Translational Sciences
Awards: G1143820356, G1146999482, G1152746180, G1172940527, G1421788377, G1766655626, A Collaborative Genomic Study of Bipolar Disorder, G2235937325, G2266261882, G2490740434, G3067535519, Washington University Institute of Clinical and Translational Sciences, G370871742, G3799582765, G3992795724, G406303579, G407586344, G4551053601, G6567415841, Collaborative Genetic Study of Bipolar Disorder, G7146893290, G7879209040, G8254808383, G8400043944, G9000221083
OpenAlex ID: W1978294328