Year: 2025
Type: article
Study design: Observational Study
Abstract: DNA methylation offers an objective method to assess the impact of smoking. In this work, we conduct a Bayesian EWAS of smoking pack years (n=17,865, ∼850k sites, Illumina EPIC array) and extend it by analysing whole genome data of smokers and non-smokers from Generation Scotland (n=46, ∼4–21 million sites via TWIST and Oxford Nanopore sequencing). We develop mCigarette, an epigenetic biomarker of smoking, and test it in three British cohorts. Results of brain- and blood-based EWAS (n brain =14, n blood =882, >450k sites, Illumina arrays) reveal several loci with near-perfect discrimination of smoking status, but which do not overlap across tissues. Furthermore, we perform a GWAS of epigenetic smoking, identifying several smoking-related loci. Overall, we improve smoking-related biomarker accuracy and enhance the understanding of the effects of smoking by integrating DNA methylation data from multiple tissues and cohorts.
Source: Nature Communications
Authors: Aleksandra D. Chybowska, Elena Bernabeu, Paul Yousefi, Matthew Suderman, Robert F. Hillary, Richard Clark, Louise MacGillivray, Lee Murphy, Sarah E. Harris, Janie Corley, Archie Campbell, Tara L. Spires-Jones, Daniel L. McCartney, Simon R. Cox, Jackie F. Price, Kathryn L. Evans, Riccardo E. Marioni
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: John Templeton Foundation, National Alliance for Research on Schizophrenia and Depression, Wellcome Trust, Scottish Government, Royal College of Physicians of Edinburgh, Alzheimer's Society, Cancer Research UK, National Institute for Health and Care Research, Scottish Funding Council, Age UK, University of Edinburgh, University of Bristol, University of Queensland, Centre for Cognitive Ageing and Cognitive Epidemiology, Directorate for Biological Sciences, Chief Scientist Office, Scottish Government Health and Social Care Directorate, Medical Research Council, Biotechnology and Biological Sciences Research Council, Economic and Social Research Council
Awards: G1131969086, G1192034430, G149876332, G1605161196, G1684393010, G1793884970, Translational Neuroscience - training the next generation of basic neuroscientists to embrace clinical research., Data mining epidemiological relationships, G1955001954, The Lothian Birth Cohort 1936 Waves 6 and 7, G235045266, G2437620908, Factors of biological ageing: does it all go together when it goes?, G259633682, G2730595978, G2864843656, Exploiting genomic approaches to identify the environmental basis of depression, G301055538, G323433674, G324601231, G339198758, G3507283293, G3522544130, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi- generation, longitudinal resource focusing on life course health and well- being., G3669141092, Molecular Epidemiology, G3831911591, G3906703801, G3987754321, G3996179666, Accessible resource for integrated epigenomics studies (ARIES), Stratifying Resilience and Depression Longitudinally (STRADL), G4434664061, The Avon Longitudinal Study for Parents and Children: An international resource for population genomic and lifecourse epidemiology. Core programme support 2014-2019., G4917231792, G4942547004, G5001017760, G5562631338, Accessible resource for integrated epigenomics studies (ARIES), Immunopsychiatry: Investigating the role of inflammation in depression and other psychiatric disorders, G666546157, G6751436026, G6868616705, A genome-wide association study of non-pathological cognitive ageing, G718988473, G738105237, The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource focusing on life course health and well-being., G824700880, G839044655, G8724570043, G8782766175, G8970456254, G9000063527, Epigenetics: Environment, Embodiment and Equality (E4)
OpenAlex ID: W4409151293