Genetic association of bipolar disorder with the β3 nicotinic receptor subunit gene

Hartz, Sarah M.; Lin, Peng-Cheng; Edenberg, Howard J.; Xuei, Xiaoling; Rochberg, Nanette; Saccone, Scott F.; Berrettini, Wade H.; Nelson, Elliot C.; Nürnberger, John I.; Bierut, Laura J.; Rice, John P.; Miller, Marvin J.; Bowman, Elizabeth S.; Rau, N. Leela; Moe, P. Ryan; Samavedy, Nalini; El‐Mallakh, Rif S.; Manji, Husseini K.; Glitz, Debra; Meyer, Eric T.; Smiley, Carrie; Foroud, Tatiana; Flury, Leah; Dick, Danielle M.; Reich, Theodore; Goate, Alison M.; McInnis, Melvin G.; DePaulo, J. Raymond; MacKinnon, Dean F.; Mondimore, Francis M.; Potash, James B.; Zandi, Peter P.; Avramopoulos, Dimitrios; Payne, Jennifer L.; Byerley, William; Vinogradov, Sophia; Coryell, William; Crowe, Raymond R.; Gershon, Elliot S.; Badner, Judith A.; Liu, Chun Yu; Sanders, Alan R.; Caserta, Maria T.; Dinwiddie, Stephen H.; Nguyen, Toan Van; Harakal, Donna; Kelsoe, John R.; McKinney, R. Anne; Scheftner, William A.; Kravitz, Howard M.; Marta, Diana H.; Vaughn-Brown, Annette; Bederow, Laurie; McMahon, Francis J.; Kassem, Layla; Detera‐Wadleigh, Sevilla D.; Austin, Lisa M.; Murphy, Dennis L.; Lawson, William B.; Nwulia, Evarista; Hipolito, Maria

doi:10.1097/ypg.0b013e32834135eb

Cited by 11 publications

(10 citation statements)

References 44 publications

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“…HTR1B , HTR3A, HTR5A, etc ) were associated with mood disorder [46]. Polymorphisms in CHRNA6 (nicotinic alpha subunit 6 of neuronal cholinergic receptor), have also been reported to be associated with bipolar disorder [47].…”

Section: Discussionmentioning

confidence: 99%

Pathway Analysis Using Information from Allele-Specific Gene Methylation in Genome-Wide Association Studies for Bipolar Disorder

Chuang

Kao²,

Shih³

et al. 2013

PLoS ONE

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Bipolar disorder (BPD) is a complex psychiatric trait with high heritability. Despite efforts through conducting genome-wide association (GWA) studies, the success of identifying susceptibility loci for BPD has been limited, which is partially attributed to the complex nature of its pathogenesis. Pathway-based analytic strategy is a powerful tool to explore joint effects of gene sets within specific biological pathways. Additionally, to incorporate other aspects of genomic data into pathway analysis may further enhance our understanding for the underlying mechanisms for BPD. Patterns of DNA methylation play important roles in regulating gene expression and function. A commonly observed phenomenon, allele-specific methylation (ASM) describes the associations between genetic variants and DNA methylation patterns. The present study aimed to identify biological pathways that are involve in the pathogenesis of BPD while incorporating brain specific ASM information in pathway analysis using two large-scale GWA datasets in Caucasian populations. A weighting scheme was adopted to take ASM information into consideration for each pathway. After multiple testing corrections, we identified 88 and 15 enriched pathways for their biological relevance for BPD in the Genetic Association Information Network (GAIN) and the Wellcome Trust Case Control Consortium dataset, respectively. Many of these pathways were significant only when applying the weighting scheme. Three ion channel related pathways were consistently identified in both datasets. Results in the GAIN dataset also suggest for the roles of extracellular matrix in brain for BPD. Findings from Gene Ontology (GO) analysis exhibited functional enrichment among genes of non-GO pathways in activity of gated channel, transporter, and neurotransmitter receptor. We demonstrated that integrating different data sources with pathway analysis provides an avenue to identify promising and novel biological pathways for exploring the underlying molecular mechanisms for bipolar disorder. Further basic research can be conducted to target the biological mechanisms for the identified genes and pathways.

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Section: Discussionmentioning

confidence: 99%

Pathway Analysis Using Information from Allele-Specific Gene Methylation in Genome-Wide Association Studies for Bipolar Disorder

Chuang

Kao²,

Shih³

et al. 2013

PLoS ONE

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“…The overrepresentation of a smoking‐related risk allele in nonsmoking schizophrenia patients remains intriguing, although an explanation is not yet clear. Interestingly, another study on association of CHRNB3 polymorphisms in bipolar disorder and nicotine addiction found that the CHRNB3 association with nicotine dependence was not different between bipolar disorder patients and the general population; although two synonymous SNPs in CHRNB3 , rs4952 and rs4953, were significantly associated with bipolar disorder even in nonsmokers (Hartz et al 2010). Petrovsky et al (2010) showed an association between CHRNA3 polymorphisms and prepulse inhibition in schizophrenia patients, although schizophrenia case vs. control association was not significant.…”

Section: Discussionmentioning

confidence: 99%

ACHRNA5allele related to nicotine addiction and schizophrenia

Hong

Yang

Wonodi

et al. 2011

Genes, Brain and Behavior

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Schizophrenia and nicotine addiction are both highly heritable phenotypes. Because individuals with schizophrenia have a higher rate of smoking than those in the general population, one could hypothesize that genes associated with smoking might be overrepresented in schizophrenia and thus help explain their increased smoking incidence. Although a number of genes have been proposed to explain the increased smoking risk in schizophrenia, none of them have been consistently linked to smoking and schizophrenia, and thus difficult to explain the increased smoking in schizophrenia. A functional smoking-related nicotinic acetylcholine receptor α5 subunit gene (CHRNA5) nonsynonymous single nucleotide polymorphism (SNP) rs16969968 (Asp398Asn) has recently been discovered and replicated. As such, we tested whether this variant contributes to smoking in schizophrenia in a sample of 313 schizophrenia patients and 525 controls. The Asp398Asn risk allele is significantly associated with smoking severity independently in schizophrenia patient smokers (P = 0.001) and control smokers (P = 0.029). Furthermore, the same risk allele is significantly associated with schizophrenia in both Caucasian (P = 0.022) and AfricanAmerican (P = 0.006) nonsmoker schizophrenia patients compared with control nonsmokers. Intriguingly, this SNP was not significantly associated with smoking status (smokers vs. nonsmokers) in either schizophrenia patients or controls. Therefore, our study identifies a genetic variant that is simultaneously linked to smoking and schizophrenia in the same cohort, but whether this SNP contributes to the increased smoking prevalence in schizophrenia patients requires additional studies.

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“…Associations between unipolar or bipolar depression and cigarette smoking may be due to biological and social-environmental factors that increase the risk of both disorders, smoking to reduce psychiatric symptoms, effects of nicotine or smoke exposure on the development of these disorders, or bidirectional causality. 81 82 83 84 85 Like smokers with schizophrenia, smokers with unipolar depression indicate that they smoke primarily to cope with craving and negative affect, and secondarily for pleasure. 62 However, they are as worried as smokers without depression about the effects of smoking on their health and equally motivated to quit.…”

Section: Unipolar and Bipolar Depressionmentioning

confidence: 99%

Smoking cessation and reduction in people with chronic mental illness

Tidey

Miller

2015

BMJ

138

105

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The high prevalence of cigarette smoking and tobacco related morbidity and mortality in people with chronic mental illness is well documented. This review summarizes results from studies of smoking cessation treatments in people with schizophrenia, depression, anxiety disorders, and post-traumatic stress disorder. It also summarizes experimental studies aimed at identifying biopsychosocial mechanisms that underlie the high smoking rates seen in people with these disorders. Research indicates that smokers with chronic mental illness can quit with standard cessation approaches with minimal effects on psychiatric symptoms. Although some studies have noted high relapse rates, longer maintenance on pharmacotherapy reduces rates of relapse without untoward effects on psychiatric symptoms. Similar biopsychosocial mechanisms are thought to be involved in the initiation and persistence of smoking in patients with different disorders. An appreciation of these common factors may aid the development of novel tobacco treatments for people with chronic mental illness. Novel nicotine and tobacco products such as electronic cigarettes and very low nicotine content cigarettes may also be used to improve smoking cessation rates in people with chronic mental illness.

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Genetic association of bipolar disorder with the β3 nicotinic receptor subunit gene

Cited by 11 publications

References 44 publications

Pathway Analysis Using Information from Allele-Specific Gene Methylation in Genome-Wide Association Studies for Bipolar Disorder

Pathway Analysis Using Information from Allele-Specific Gene Methylation in Genome-Wide Association Studies for Bipolar Disorder

ACHRNA5allele related to nicotine addiction and schizophrenia

Smoking cessation and reduction in people with chronic mental illness

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