ArticleScientific reports2021
Analyses of nicotine metabolism biomarker genetics stratified by sex in African and European Americans.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 13 papers.
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.
Enhancing Tobacco Use Treatment for African American Light Smokers
Pharmacogenetics of Nicotine Addiction Treatment (PNAT)
Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Sex dependent genetic architecture of biochemically verified tobacco use.Psychiatry research · 2025Trial
- Genetic Prediction of Smoking Cessation Medication Side Effects: A Genome-Wide Investigation of Abnormal Dreams on Varenicline.Clinical pharmacology and therapeutics · 2024Trial
- Nicotine-Mediated Redox and Nitrosative Stress in Cardiorenal Health.Hypertension (Dallas, Tex. : 1979) · 2026Review
- Sex, hormones, and lung health.Physiological reviews · 2026Review
- Trends in influenza- and pneumonia-related mortality in lung cancer patients from 1999 to 2022: a retrospective CDC WONDER analysis.Respiratory research · 2025Article
- Examining the Role of Race/Ethnicity and Sex in Modifying the Association Between Early Smoking Initiation and Mortality: A 20-Year NHANES Analysis.AJPM focus · 2025Article
- Urinary anatalline and nicotelline cut-points to distinguish between exclusive and dual use of tobacco products.Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals · 2024Article
- Association of Urinary Biomarkers of Tobacco Exposure with Lung Cancer Risk in African American and White Cigarette Smokers in the Southern Community Cohort Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2024Article
- Sex Differences in Lung Cancer.Cancers · 2023Review
- The use of biomarkers to guide precision treatment for tobacco use.Addiction neuroscience · 2023Article
- Influence of CYP2A6 Genetic Variation, Nicotine Dependence Severity, and Treatment on Smoking Cessation Success.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2023Article
- Predicting nicotine metabolism across ancestries using genotypes.BMC genomics · 2022Article
- Genetic influences impacting nicotine use and abuse during adolescence: Insights from human and rodent studies.Brain research bulletin · 2022Review
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
Abstract
Nicotine is inactivated by the polymorphic CYP2A6 enzyme to cotinine and then to 3'hydroxycotinine. The Nicotine Metabolite Ratio (NMR; 3'hydroxycotinine/cotinine) is a heritable nicotine metabolism biomarker, varies with sex and ancestry, and influences smoking cessation and disease risk. We conducted sex-stratified genome-wide association studies of the NMR in European American (EA) and African American (AA) smokers (NCT01314001, NCT00666978). In EA females (n = 389) and males (n = 541), one significant (P < 5e-8) chromosome 19 locus was found (top variant: rs56113850, CYP2A6 (intronic), for C vs. T: females: beta = 0.67, P = 7.5e-22, 21.8% variation explained; males: beta = 0.75, P = 1.2e-37, 26.1% variation explained). In AA females (n = 503) and males (n = 352), the top variant was found on chromosome 19 but differed by sex (females: rs11878604, CYP2A6 (~ 16 kb 3'), for C vs. T: beta = - 0.71, P = 6.6e-26, 16.2% variation explained; males: rs3865454, CYP2A6 (~ 7 kb 3'), for G vs. T: beta = 0.64, P = 1.9e-19, 18.9% variation explained). In AA females, a significant region was found on chromosome 12 (top variant: rs12425845: P = 5.0e-9, TMEM132C (~ 1 Mb 5'), 6.1% variation explained) which was not significant in AA males. In AA males, significant regions were found on chromosomes 6 (top variant: rs9379805: P = 4.8e-9, SLC17A2 (~ 8 kb 5'), 8.0% variation explained) and 16 (top variant: rs77368288: P = 3.5e-8, ZNF469 (~ 92 kb 5'), 7.1% variation explained) which were not significant in AA females. Further investigation of these associations outside of chromosome 19 is required, as they did not replicate. Understanding how sex and ancestry influence nicotine metabolism genetics may improve personalized approaches for smoking cessation and risk prediction for tobacco-related diseases.
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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.