ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2010
Variation in the nicotinic acetylcholine receptor gene cluster CHRNA5-CHRNA3-CHRNB4 and its interaction with recent tobacco use influence cognitive flexibility.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 29 citations in OpenAlex.
- Investigating the role of eight SNPs inAnnals of medicine · 2025Article
- Association of SNPs in nAChRs genes, areca nut chewing and smoking, and their interaction with lung cancer in Hainan, China: a case control study.BMC cancer · 2025Article
- α3* Nicotinic Acetylcholine Receptors in the Habenula-Interpeduncular Nucleus Circuit Regulate Nicotine Intake.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Differential Expression Patterns of Lynx Proteins and Involvement of Lynx1 in Prepulse Inhibition.Frontiers in behavioral neuroscience · 2021Article
- Multidimensional Intersection of Nicotine, Gene Expression, and Behavior.Frontiers in behavioral neuroscience · 2021Article
- Identification of susceptibility variants to benign childhood epilepsy with centro-temporal spikes (BECTS) in Chinese Han population.EBioMedicine · 2020Article
- Identification of CHRNB4 as a Diagnostic/Prognostic Indicator and Therapeutic Target in Human Esophageal Squamous Cell Carcinoma.Frontiers in oncology · 2020Article
- Adverse Childhood Experiences, Epigenetic Measures, and Obesity in Youth.The Journal of pediatrics · 2018Article
- Effect of genetic variation in the nicotinic receptor genes on risk for posttraumatic stress disorder.Psychiatry research · 2015Article
- The DYX2 locus and neurochemical signaling genes contribute to speech sound disorder and related neurocognitive domains.Genes, brain, and behavior · 2015Article
- Hippocampal changes produced by overexpression of the human CHRNA5/A3/B4 gene cluster may underlie cognitive deficits rescued by nicotine in transgenic mice.Acta neuropathologica communications · 2014Article
- Role of a genetic variant on the 15q25.1 lung cancer susceptibility locus in smoking-associated nasopharyngeal carcinoma.PloS one · 2014Article
- Nicotinic receptor gene variants interact with attention deficient hyperactive disorder symptoms to predict smoking trajectories from early adolescence to adulthood.Addictive behaviors · 2013Article
- Lack of association between COMT and working memory in a population-based cohort of healthy young adults.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2013Article
- Variants in the 15q25 gene cluster are associated with risk for schizophrenia and bipolar disorder.Psychiatric genetics · 2013Article
- Article
- Pharmacogenetics of smoking cessation: role of nicotine target and metabolism genes.Human genetics · 2012Article
- Differences in delay discounting between smokers and nonsmokers remain when both rewards are delayed.Psychopharmacology · 2012Article
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4 authors at 3 institutions in 1 country.
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Abstract
Variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster have been associated with nicotine dependence (ND) and ND-related traits. To evaluate a potential underlying mechanism for this association, we investigated the effects of 10 variants in this gene cluster and their interactive effects as a result of recent smoking on cognitive flexibility, a possible mediator of genetic effects in smokers. Cognitive flexibility of 466 European Americans (EAs; 360 current smokers) and 805 African Americans (AAs; 635 current smokers) was assessed using the Wisconsin Card Sorting Test. The main effects of variants and haplotypes and their interaction with recent smoking on cognitive flexibility were examined using multivariate analysis of variance and the haplotype analysis program HAPSTAT. In EAs, the major alleles of five variants (CHRNA5-rs3841324-22 bp-insertion-allele, CHRNA5-rs615470-C-allele, CHRNA3-rs6495307-C-allele, CHRNA3-rs2869546-T-allele, and CHRNB4-rs11637890-C-allele) were associated with significantly greater perseverative responses (P=0.003-0.017) and perseverative errors (P=0.004-0.026; recessive effect). Among EAs homozygous for the major alleles of each of these five variants, current smokers made fewer perseverative responses and perseverative errors than did past smokers. Significant interactive effects of four variants (rs3841324, rs615470, rs6495307, and rs2869546) and current smoking on cognitive flexibility were observed (perseverative responses (P=0.010-0.044); perseverative errors (P=0.017-0.050)). However, in AAs, 10 variants in this gene cluster showed no apparent effects on cognitive flexibility. These findings suggest that variation in the CHRNA5-CHRNA3-CHRNB4 gene cluster influences cognitive flexibility differentially in AAs and EAs and that current smoking moderates this effect. These findings could account in part for differences in ND risk associated with these variants in AAs and EAs.
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