Association of the serotonin transporter gene, neuroticism and smoking behaviours

O’Gara, Colin; Knight, Jo; Stapleton, John; Luty, Jason; Neale, B. M.; Nash, M W; Heuzo-Diaz, P.; Hoda, Farzana; Cohen, Sarah S.; Collier, David; Sham, Pak C.; Ball, David; McGuffin, Peter; Craig, Ian W.

doi:10.1007/s10038-007-0243-1

Cited by 16 publications

(14 citation statements)

References 54 publications

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“…Serotonin receptor signaling was enriched in the genes associated with SI/P and ND, but not SC, in our analysis. In several recent studies designed to investigate the association between genes from the serotonin receptor signaling pathway and SC, no positive result was obtained (Brody et al , 2005; David et al , 2008a; David et al , 2007b; Munafo et al , 2006; O'Gara et al , 2008). Similar to the serotonin receptor signaling pathway, tryptophan metabolism, the pathway involved in the biological synthesis of serotonin, is enriched in the genes associated with SI/P, but not in SC.…”

Section: Discussionmentioning

confidence: 99%

Common and Unique Biological Pathways Associated with Smoking Initiation/Progression, Nicotine Dependence, and Smoking Cessation

Wang

2009

Neuropsychopharmacol

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Twin and family studies reveal a significant genetic contribution to the risk of smoking initiation and progression (SI/P), nicotine dependence (ND), and smoking cessation (SC). Further, numerous genes have been implicated in these smoking-related behaviors, especially for ND. However, no study has presented a comprehensive and systematic view of the genetic factors associated with these important smoking-related phenotypes. By reviewing the literature on these behaviors, we identified 16, 99, and 75 genes that have been associated with SI/P, ND, and SC, respectively. We then determined whether these genes were enriched in pathways important in the neuronal and brain functions underlying addiction. We identified 9, 21, and 13 pathways enriched in the genes associated with SI/P, ND, and SC, respectively. Among these pathways, four were common to all of the three phenotypes; i.e., calcium signaling, cAMP-mediated signaling, dopamine receptor signaling, and G-protein-coupled receptor signaling. Further, we found that serotonin receptor signaling and tryptophan metabolism pathways were shared by SI/P and ND, tight junction signaling pathway was shared by SI/P and SC, and gap junction, neurotrophin/TRK signaling, synaptic long-term potentiation, and tyrosine metabolism were shared between ND and SC. Together, these findings demonstrate significant genetic overlap among these three related phenotypes. Although identification of susceptibility genes for smoking-related behaviors is still in an early stage, the approach utilized in this study has potential to overcome the hurdles caused by factors such as genetic heterogeneity and small sample size, and thus should yield greater insights into the genetic mechanisms underlying these complex phenotypes.

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Section: Discussionmentioning

confidence: 99%

Common and Unique Biological Pathways Associated with Smoking Initiation/Progression, Nicotine Dependence, and Smoking Cessation

Wang

2009

Neuropsychopharmacol

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“…Data suggested also that smoking behavior is influenced by an interaction between neuroticism and 5-HTTLPR genotype [ 32 ]. More recently, however, a number of studies demonstrated that although neuroticism and depression vulnerability were associated with smoking behavior, genotype did not affect this relationship [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Lack of association between serotonin transporter gene polymorphism 5-HTTLPR and smoking among Polish population: a case-control study

et al. 2008

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Background: A better understanding of the genetic determinants of tobacco smoking might help in developing more effective cessation therapies, tailored to smokers' genotype. Insertion/deletion polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been linked to vulnerability to smoking and ability to quit. We aimed to determine whether 5-HTTLPR genotype is associated with smoking behavior in Caucasians from Northern Poland and to investigate other risk factors for tobacco smoking.

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“…A ‘reward deficiency syndrome’ has been postulated as one unifying theme to account for the role of diverse neurotransmitters in nicotine dependency [25], [26], [27], and consequently many studies have evaluated genes in opioid [28], [29], serotinergic [30], [31], [32], dopaminergic [26], [33], [34], [35], drug metabolizing enzyme [36], [37], [38], [39], [40], [41] and nicotinic and muscarinic cholinergic receptor pathways[42], [43]. Results from these studies have been largely equivocal, due to small sample sizes in individual studies, incomplete and non-overlapping genetic coverage, differences in measures of smoking behavior, or differences in genetic and environmental backgrounds.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide and Candidate Gene Association Study of Cigarette Smoking Behaviors

Caporaso¹,

Chatterjee³

et al. 2009

PLoS ONE

231

180

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The contribution of common genetic variation to one or more established smoking behaviors was investigated in a joint analysis of two genome wide association studies (GWAS) performed as part of the Cancer Genetic Markers of Susceptibility (CGEMS) project in 2,329 men from the Prostate, Lung, Colon and Ovarian (PLCO) Trial, and 2,282 women from the Nurses' Health Study (NHS). We analyzed seven measures of smoking behavior, four continuous (cigarettes per day [CPD], age at initiation of smoking, duration of smoking, and pack years), and three binary (ever versus never smoking, ≤10 versus >10 cigarettes per day [CPDBI], and current versus former smoking). Association testing for each single nucleotide polymorphism (SNP) was conducted by study and adjusted for age, cohabitation/marital status, education, site, and principal components of population substructure. None of the SNPs achieved genome-wide significance (p<10−7) in any combined analysis pooling evidence for association across the two studies; we observed between two and seven SNPs with p<10−5 for each of the seven measures. In the chr15q25.1 region spanning the nicotinic receptors CHRNA3 and CHRNA5, we identified multiple SNPs associated with CPD (p<10−3), including rs1051730, which has been associated with nicotine dependence, smoking intensity and lung cancer risk. In parallel, we selected 11,199 SNPs drawn from 359 a priori candidate genes and performed individual-gene and gene-group analyses. After adjusting for multiple tests conducted within each gene, we identified between two and five genes associated with each measure of smoking behavior. Besides CHRNA3 and CHRNA5, MAOA was associated with CPDBI (gene-level p<5.4×10−5), our analysis provides independent replication of the association between the chr15q25.1 region and smoking intensity and data for multiple other loci associated with smoking behavior that merit further follow-up.

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Association of the serotonin transporter gene, neuroticism and smoking behaviours

Cited by 16 publications

References 54 publications

Common and Unique Biological Pathways Associated with Smoking Initiation/Progression, Nicotine Dependence, and Smoking Cessation

Common and Unique Biological Pathways Associated with Smoking Initiation/Progression, Nicotine Dependence, and Smoking Cessation

Lack of association between serotonin transporter gene polymorphism 5-HTTLPR and smoking among Polish population: a case-control study

Genome-Wide and Candidate Gene Association Study of Cigarette Smoking Behaviors

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