ArticlePloS one2014
Massive withdrawal symptoms and affective vulnerability are associated with variants of the CHRNA4 gene in a subgroup of smokers.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- Correlates of nicotine withdrawal severity in smokers during a smoke-free psychiatric hospitalization.Preventive medicine · 2016Trial
- Coordination among frequent genetic variants imparts substance use susceptibility and pathogenesis.Frontiers in neuroscience · 2024Article
- Genetic association of human Corticotropin-Releasing Hormone Receptor 1 (CRHR1) with Internet gaming addiction in Korean male adolescents.BMC psychiatry · 2018Article
- Pathways to precision medicine in smoking cessation treatments.Neuroscience letters · 2018Review
- African-specific variability in the acetylcholine muscarinic receptor M4: association with cocaine and heroin addiction.Pharmacogenomics · 2016Article
- Nicotinic acetylcholine receptors: upregulation, age-related effects and associations with drug use.Genes, brain, and behavior · 2016Review
- Withdrawal: Expanding a Key Addiction Construct.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2015Review
- A Genome-Wide Association Study of Emphysema and Airway Quantitative Imaging Phenotypes.American journal of respiratory and critical care medicine · 2015Article
- Nicotinic receptor modulation to treat alcohol and drug dependence.Frontiers in neuroscience · 2014Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterogeneous phenotypes of complex disorders pose a great challenge for genetic association studies and for the development of personalized treatment strategies. Cluster analysis of phenotypic data has been recently proposed as a reliable auxiliary method for such studies. A cohort of 236 treatment-seeking smokers was investigated after overnight nicotine abstinence. Alpha4 nicotinic acetylcholine receptor (nAChR) subunit-related phenotypes were assessed by the Fagerström Test for Nicotine Dependence (FTND), exhaled carbon monoxide (CO) measurements, the Minnesota Nicotine Withdrawal Scale (MNWS) and the Zung Self-Rating Depression Scale (ZSDS). Seven tag SNPs (single-nucleotide polymorphisms) across CHRNA4 (the gene encoding alpha4 subunit of the nicotinic acetylcholine receptor) were genotyped and two-step cluster analysis was used for phenotypic cluster characterization. Haplotype estimation was determined by HapStat module of R 2.0 software. Three different phenotypic clusters were identified and the C3 cluster was characterized by the highest ZSDS and MNWS scores compared to others. Furthermore, lifetime prevalence of major depression was significantly higher in the C3 cluster (p = 0.019). In genetic association tests, this cluster was also significantly associated with rs3787138 genotypes (p = 0.004) while haplotype analyses of three SNPs (rs3787138, rs1044396, rs3787140) revealed that the risk for C3 phenotype was almost three times higher in GCC haplotype carriers compared to others (pperm = 0.013). This is the first report on a significant association between CHRNA4 variants and a subgroup of smokers characterized by massive withdrawal symptoms and affective vulnerability. Identification of such a phenotypic cluster can be a pivotal step for further pharmacogenetic studies on ligands of the alpha4 nAChR subunit. Our results suggest that performing cluster analysis in genetic association studies can be proposed for complex disorders.
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