ArticlePLoS genetics2015
A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 5 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
82 citing papers in PubMed, 5 syntheses or guidelines pooled it, 124 citations in OpenAlex.
- Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent.Molecular psychiatry · 2021Pooled it
- Genome-wide association study of smoking trajectory and meta-analysis of smoking status in 842,000 individuals.Nature communications · 2020Pooled it
- Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.Molecular psychiatry · 2020Pooled it
- Use of polygenic risk scores of nicotine metabolism in predicting smoking behaviors.Pharmacogenomics · 2018Pooled it
- Pathways to smoking behaviours: biological insights from the Tobacco and Genetics Consortium meta-analysis.Molecular psychiatry · 2017Pooled it
- Opioid Use and Rate of Nicotine Metabolism Among Pregnant Smokers.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2020Trial
- Association of Reduced Nicotine Content Cigarettes With Smoking Behaviors and Biomarkers of Exposure Among Slow and Fast Nicotine Metabolizers: A Nonrandomized Clinical Trial.JAMA network open · 2018Trial
- Nicotine metabolites generate craniofacial defects that are worsened by ethanol exposure.PNAS nexus · 2026Article
- Nicotine metabolite ratio and clinically significant depressive symptoms in U.S. adults: A smoker-specific association.Medicine · 2026Observational
- Dietary caffeine to assess CYP1A2 activity, tailor clozapine doses, and predict treatment response: genetic, epigenetic and clinical analyses.Molecular psychiatry · 2026Article
- Disentangling Nicotine vs Non-Nicotine Components of Tobacco Exposure in Psoriasis and Psoriatic Arthritis: A Multivariable and Trans-Ethnic Mendelian Randomization Study.Clinical, cosmetic and investigational dermatology · 2026Article
- A phenome-wide association study of genetically determined nicotine metabolism reveals novel links with health-related outcomes.European journal of epidemiology · 2025Article
- Extending Investigations of miR-126-5p on the Regulation of CYP2A6, the Major Nicotine-Inactivating Enzyme.Pharmacology research & perspectives · 2025Article
- Fine-mapping the CYP2A6 regional association with nicotine metabolism among African American smokers.Molecular psychiatry · 2025Article
- Nicotine Metabolism-Related Genetic Polymorphisms Associated with Smoking Cessation in Korean Men: A Candidate Gene Association Study in a Korean Cohort.Lifestyle genomics · 2025Article
- Considerations for the application of polygenic scores to clinical care of individuals with substance use disorders.The Journal of clinical investigation · 2024Review
- CYP2A6 Activity and Cigarette Consumption Interact in Smoking-Related Lung Cancer Susceptibility.Cancer research · 2024Article
- CYP2A6 associates with respiratory disease risk and younger age of diagnosis: a phenome-wide association Mendelian Randomization study.Human molecular genetics · 2024Article
- An in-depth association analysis of genetic variants within nicotine-related loci: Meeting in middle of GWAS and genetic fine-mapping.Molecular and cellular neurosciences · 2023Article
- Can Treatment Support Mitigate Nicotine Metabolism-Based Disparities in Smoking Abstinence? Secondary Analysis of the Helping HAND 4 Trial.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2023Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 9 institutions in 4 countries.
Funding
Abstract
Individuals with fast nicotine metabolism typically smoke more and thus have a greater risk for smoking-induced diseases. Further, the efficacy of smoking cessation pharmacotherapy is dependent on the rate of nicotine metabolism. Our objective was to use nicotine metabolite ratio (NMR), an established biomarker of nicotine metabolism rate, in a genome-wide association study (GWAS) to identify novel genetic variants influencing nicotine metabolism. A heritability estimate of 0.81 (95% CI 0.70-0.88) was obtained for NMR using monozygotic and dizygotic twins of the FinnTwin cohort. We performed a GWAS in cotinine-verified current smokers of three Finnish cohorts (FinnTwin, Young Finns Study, FINRISK2007), followed by a meta-analysis of 1518 subjects, and annotated the genome-wide significant SNPs with methylation quantitative loci (meQTL) analyses. We detected association on 19q13 with 719 SNPs exceeding genome-wide significance within a 4.2 Mb region. The strongest evidence for association emerged for CYP2A6 (min p = 5.77E-86, in intron 4), the main metabolic enzyme for nicotine. Other interesting genes with genome-wide significant signals included CYP2B6, CYP2A7, EGLN2, and NUMBL. Conditional analyses revealed three independent signals on 19q13, all located within or in the immediate vicinity of CYP2A6. A genetic risk score constructed using the independent signals showed association with smoking quantity (p = 0.0019) in two independent Finnish samples. Our meQTL results showed that methylation values of 16 CpG sites within the region are affected by genotypes of the genome-wide significant SNPs, and according to causal inference test, for some of the SNPs the effect on NMR is mediated through methylation. To our knowledge, this is the first GWAS on NMR. Our results enclose three independent novel signals on 19q13.2. The detected CYP2A6 variants explain a strikingly large fraction of variance (up to 31%) in NMR in these study samples. Further, we provide evidence for plausible epigenetic mechanisms influencing NMR.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.