ArticleHuman molecular genetics2012
Use of a predictive model derived from in vivo endophenotype measurements to demonstrate associations with a complex locus, CYP2A6.
Article in Human molecular genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
32 citing papers in PubMed, 5 syntheses or guidelines pooled it, 35 citations in OpenAlex.
- Nicotine Metabolism Predicted by CYP2A6 Genotypes in Relation to Smoking Cessation: A Systematic Review.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Pooled it
- Use of polygenic risk scores of nicotine metabolism in predicting smoking behaviors.Pharmacogenomics · 2018Pooled it
- From genes to treatments: a systematic review of the pharmacogenetics in smoking cessation.Pharmacogenomics · 2018Pooled it
- Pharmacotherapy for smoking cessation: effects by subgroup defined by genetically informed biomarkers.The Cochrane database of systematic reviews · 2017Pooled it
- Risk loci for chronic obstructive pulmonary disease: a genome-wide association study and meta-analysis.The Lancet. Respiratory medicine · 2014Pooled it
- Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups.Carcinogenesis · 2014Trial
- Beyond cigarettes per day. A genome-wide association study of the biomarker carbon monoxide.Annals of the American Thoracic Society · 2014Trial
- Pharmacotherapy effects on smoking cessation vary with nicotine metabolism gene (CYP2A6).Addiction (Abingdon, England) · 2014Trial
- CYP2A6 associates with respiratory disease risk and younger age of diagnosis: a phenome-wide association Mendelian Randomization study.Human molecular genetics · 2024Article
- Inhibition of Nicotine Metabolism by Cannabidiol (CBD) and 7-Hydroxycannabidiol (7-OH-CBD).Chemical research in toxicology · 2023Article
- Evaluation of a weighted genetic risk score for the prediction of biomarkers of CYP2A6 activity.Addiction biology · 2020Article
- Strain-specific altered nicotine metabolism in 3,3'-diindolylmethane (DIM) exposed mice.Biopharmaceutics & drug disposition · 2019Article
- Nicotine oxidation by genetic variants of CYP2B6 and in human brain microsomes.Pharmacology research & perspectives · 2019Article
- Prevalence of Some Genetic Risk Factors for Nicotine Dependence in Ukraine.Genetics research international · 2019Article
- Pathways to precision medicine in smoking cessation treatments.Neuroscience letters · 2018Review
- The Value of Biosamples in Smoking Cessation Trials: A Review of Genetic, Metabolomic, and Epigenetic Findings.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2018Review
- Nicotine dependence is associated with functional variation in FMO3, an enzyme that metabolizes nicotine in the brain.The pharmacogenomics journal · 2018Article
- CYP2A6 metabolism in the development of smoking behaviors in young adults.Addiction biology · 2018Article
- 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
- CYP2A6 genetic polymorphisms and biomarkers of tobacco smoke constituents in relation to risk of lung cancer in the Singapore Chinese Health Study.Carcinogenesis · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
This study demonstrates a novel approach to test associations between highly heterogeneous genetic loci and complex phenotypes. Previous investigations of the relationship between Cytochrome P450 2A6 (CYP2A6) genotype and smoking phenotypes made comparisons by dividing subjects into broad categories based on assumptions that simplify the range of function of different CYP2A6 alleles, their numerous possible diplotype combinations and non-additive allele effects. A predictive model that translates CYP2A6 diplotype into a single continuous variable was previously derived from an in vivo metabolism experiment in 189 European Americans. Here, we apply this model to assess associations between genotype, inferred nicotine metabolism and smoking behaviors in larger samples without direct nicotine metabolism measurements. CYP2A6 genotype is not associated with nicotine dependence, as defined by the Fagerström Test of Nicotine Dependence, demonstrating that cigarettes smoked per day (CPD) and nicotine dependence have distinct genetic correlates. The predicted metric is significantly associated with CPD among African Americans and European American dependent smokers. Individual slow metabolizing genotypes are associated with lower CPD, but the predicted metric is the best predictor of CPD. Furthermore, optimizing the predictive model by including additional CYP2A6 alleles improves the fit of the model in an independent data set and provides a novel method of predicting the functional impact of alleles without direct metabolism measurements. Lastly, comprehensive genotyping and in vivo metabolism data are used to demonstrate that genome-wide significant associations between CPD and single nucleotide polymorphisms are the result of synthetic associations.
Indexed as
Identifiers
What OpenQuestion holds
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.