SynthesisMolecular psychiatry2021
Genome-wide association meta-analysis of nicotine metabolism and cigarette consumption measures in smokers of European descent.
Synthesis in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 4 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
43 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Dissecting the Genetic Architecture of Intracranial Aneurysms.Circulation. Genomic and precision medicine · 2025Pooled it
- Genetic susceptibility to caffeine intake and metabolism: a systematic review.Journal of translational medicine · 2024Pooled it
- The Promise of Polygenic Risk Prediction in Smoking Cessation: Evidence From Two Treatment Trials.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Pooled it
- Pooled it
- Sex dependent genetic architecture of biochemically verified tobacco use.Psychiatry research · 2025Trial
- Genetic Basis of Tobacco Use Disorder.Genes · 2026Review
- A cross-ancestry genetic atlas of shared susceptibility between infectious diseases and cancer.Functional & integrative genomics · 2026Article
- Nicotine-Mediated Redox and Nitrosative Stress in Cardiorenal Health.Hypertension (Dallas, Tex. : 1979) · 2026Review
- Faster CYP2A6 increases COPD and lung cancer risk by increasing smoking quantity: a mediated mendelian randomization and observational mediation study.Respiratory research · 2026Observational
- Genetic and Proteomic Investigation of the Smoking-Parkinson's Disease Association.medRxiv : the preprint server for health sciences · 2026Article
- Nicotine Metabolism and Chronic Obstructive Pulmonary Disease: Mendelian Randomization and Phenotypic Characterization Analysis.International journal of chronic obstructive pulmonary disease · 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
- Multi-ancestral genome-wide association study of clinically defined nicotine dependence reveals strong genetic correlations with other substance use disorders and health-related traits.Psychological medicine · 2025Article
- Differences and similarities between the genetic architecture of lifetime substance use across different substances.Psychological medicine · 2025Article
- Disentangling the effects of nicotine versus non-nicotine constituents of tobacco smoke on major depressive disorder: A multivariable Mendelian randomisation study.Addiction (Abingdon, England) · 2025Article
- Article
- Effect of very low nicotine content cigarettes on smoking behavior in Chinese smokers with genotype-stratified nicotine metabolism rates.Frontiers in psychiatry · 2025Article
- Integrating genetic and clinical data to predict lung cancer in patients with chronic obstructive pulmonary disease.BMC pulmonary medicine · 2024Article
- PharmVar GeneFocus: CYP2A6.Clinical pharmacology and therapeutics · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors.
Funding
Abstract
Smoking behaviors, including amount smoked, smoking cessation, and tobacco-related diseases, are altered by the rate of nicotine clearance. Nicotine clearance can be estimated using the nicotine metabolite ratio (NMR) (ratio of 3'hydroxycotinine/cotinine), but only in current smokers. Advancing the genomics of this highly heritable biomarker of CYP2A6, the main metabolic enzyme for nicotine, will also enable investigation of never and former smokers. We performed the largest genome-wide association study (GWAS) to date of the NMR in European ancestry current smokers (n = 5185), found 1255 genome-wide significant variants, and replicated the chromosome 19 locus. Fine-mapping of chromosome 19 revealed 13 putatively causal variants, with nine of these being highly putatively causal and mapping to CYP2A6, MAP3K10, ADCK4, and CYP2B6. We also identified a putatively causal variant on chromosome 4 mapping to TMPRSS11E and demonstrated an association between TMPRSS11E variation and a UGT2B17 activity phenotype. Together the 14 putatively causal SNPs explained ~38% of NMR variation, a substantial increase from the ~20 to 30% previously explained. Our additional GWASs of nicotine intake biomarkers showed that cotinine and smoking intensity (cotinine/cigarettes per day (CPD)) shared chromosome 19 and chromosome 4 loci with the NMR, and that cotinine and a more accurate biomarker, cotinine + 3'hydroxycotinine, shared a chromosome 15 locus near CHRNA5 with CPD and Pack-Years (i.e., cumulative exposure). Understanding the genetic factors influencing smoking-related traits facilitates epidemiological studies of smoking and disease, as well as assists in optimizing smoking cessation support, which in turn will reduce the enormous personal and societal costs associated with smoking.
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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 Socratic graph.