EpiSmokEr2: a robust epigenetic classifier for smoking status inference using Illumina EPIC methylation data
Year: 2026
Type: article
Abstract: AIM: Tobacco smoking induces persistent DNA methylation (DNAm) changes in blood that can serve as long-term biomarkers for smoking exposure. We aimed to develop and validate a DNAm classifier of smoking status using Illumina EPIC array data. METHODS: We built Epigenetic Smoking status Estimator2 (EpiSmokEr2), a Least Absolute Shrinkage and Selection Operator (LASSO) regression-based DNAm classifier using 511 CpGs from Illumina Infinium MethylationEPIC array (EPIC) data. The model was trained on 1343 samples from the Young Finns Study cohort and validated across six independent datasets from four cohorts and two array platforms (EPIC and EPICv2). RESULTS: EpiSmokEr2 achieved an average sensitivity of 0.87 and specificity of 0.86 in distinguishing current from never smokers. Predicted smoking status correlated strongly with established DNAm smoking scores and GrimAge, indicating its ability to capture biologically relevant smoking effects. Simulation analysis showed EpiSmokEr2 was robust for up to 10% missing CpGs. CONCLUSION: EpiSmokEr2 provides a reliable DNAm-based estimator of smoking status. It is available as an open-source R package on GitHub, facilitating broad use in epidemiological and clinical research.
Source: Epigenomics
Authors: Tianyu Zhu, Teodóra Faragó, Sailalitha Bollepalli, Aino Heikkinen, Mikaela Hukkanen, Olli Raitakari, Terho Lehtimäki, Tellervo Korhonen, Jaakko Kaprio, Fang Fang, Kaitlyn G. Lawrence, Dale P. Sandler, Mari Roberts Spildrejorde, Kristina Gervin, Yanyu Pan, Ricardo Costeira, Jordana T Bell, Miina Ollikainen
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: U.S. Department of Health and Human Services, Foundation for Cardiovascular Research, Yrjö Jahnssonin Säätiö, Wellcome Trust, Chronic Disease Research Foundation, National Institute for Health and Care Research, King's College London, European Commission, Kela, Academy of Finland, Suomen Kulttuurirahasto, Jane ja Aatos Erkon Säätiö, Juho Vainion Säätiö, Signe ja Ane Gyllenbergin Säätiö, Emil Aaltosen Säätiö, Norges Forskningsråd, Sydäntutkimussäätiö, Tampereen Tuberkuloosisäätiö, Diabetesliitto, Paavo Nurmen Säätiö, Tays, Syöpäsäätiö, Versus Arthritis, Suomen kliinisen kemian yhdistys, National Institutes of Health, Medical Research Council, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, Economic and Social Research Council, National Institute on Drug Abuse, H2020 European Research Council
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OpenAlex ID: W7129739874