ArticleMolecular psychiatry2016
A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences.
Article in Molecular psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 4 of them syntheses that pooled it.
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Who cites it
20 citing papers in PubMed, 4 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Exome Chip Meta-analysis Fine Maps Causal Variants and Elucidates the Genetic Architecture of Rare Coding Variants in Smoking and Alcohol Use.Biological psychiatry · 2019Pooled it
- Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.Nature genetics · 2019Pooled it
- Genome-wide association study across European and African American ancestries identifies a SNP in DNMT3B contributing to nicotine dependence.Molecular psychiatry · 2018Pooled it
- Genome-wide meta-analysis reveals common splice site acceptor variant in CHRNA4 associated with nicotine dependence.Translational psychiatry · 2015Pooled it
- Translational genomic research: the role of genetic polymorphisms in MBSR program among breast cancer survivors (MBSR[BC]).Translational behavioral medicine · 2019Trial
- Genetic Basis of Tobacco Use Disorder.Genes · 2026Review
- Gene-based burden tests of rare germline variants identify six cancer susceptibility genes.Nature genetics · 2024Article
- Systematic review and meta-analysis of the genetics of peripheral arterial disease.JVS-vascular science · 2024Review
- Hedgehog-interacting protein acts in the habenula to regulate nicotine intake.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Genetic influences impacting nicotine use and abuse during adolescence: Insights from human and rodent studies.Brain research bulletin · 2022Review
- Functional characterization of novel rare CYP2A6 variants and potential implications for clinical outcomes.Clinical and translational science · 2022Article
- Methylome and transcriptome signature of bronchoalveolar cells from multiple sclerosis patients in relation to smoking.Multiple sclerosis (Houndmills, Basingstoke, England) · 2021Article
- Variance explained by whole genome sequence variants in coding and regulatory genome annotations for six dairy traits.BMC genomics · 2018Article
- Human Genetics of Addiction: New Insights and Future Directions.Current psychiatry reports · 2018Review
- Peripheral Arterial Disease Genetics: Progress to Date and Challenges Ahead.Current cardiology reports · 2017Review
- The genetic epidemiology of substance use disorder: A review.Drug and alcohol dependence · 2017Review
- Sequence variants in ARHGAP15, COLQ and FAM155A associate with diverticular disease and diverticulitis.Nature communications · 2017Article
- Neuropeptide systems and new treatments for nicotine addiction.Psychopharmacology · 2017Review
- A Novel Tobacco Use Phenotype Suggests the 15q25 and 19q13 Loci May be Differentially Associated With Cigarettes per Day and Tobacco-Related Problems.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2017Article
- "Gestaltomics": Systems Biology Schemes for the Study of Neuropsychiatric Diseases.Frontiers in physiology · 2017Review
Corrections and comments
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Authors and funding
35 authors at 11 institutions in 7 countries.
Funding
Abstract
Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency=0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P=1.2 × 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P=4.0 × 10(-4)), chronic obstructive pulmonary disease (COPD; P=9.3 × 10(-4)), peripheral artery disease (PAD; P=0.090) and abdominal aortic aneurysms (AAAs; P=0.12), and the variant associates strongly with the early-onset forms of LC (OR=4.49, P=2.2 × 10(-4)), COPD (OR=3.22, P=2.9 × 10(-4)), PAD (OR=3.47, P=9.2 × 10(-3)) and AAA (OR=6.44, P=6.3 × 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P=6.8 × 10(-5)), particularly for early-onset cases (P=2.1 × 10(-7)). Our results are in agreement with functional studies showing that the human α4β2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.
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Registered trials
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