A blood- and brain-based EWAS of smoking
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 two British cohorts. Results of brain- and blood-based EWAS (n<sub>brain</sub>=14, n<sub>blood</sub> = 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.
Authors
- Lee Murphy (ORCID: https://orcid.org/0000-0001-6467-7449)
- Jackie F. Price (ORCID: https://orcid.org/0000-0003-3251-3970)
- Paul Yousefi (ORCID: https://orcid.org/0000-0003-3284-3240)
- Archie Campbell (ORCID: https://orcid.org/0000-0003-0198-5078)
- Kathryn L. Evans (ORCID: https://orcid.org/0000-0002-7884-5877)
- Sarah E. Harris (ORCID: https://orcid.org/0000-0002-4941-5106)
- Daniel L. McCartney (ORCID: https://orcid.org/0000-0003-3242-0360)
- Matthew Suderman (ORCID: https://orcid.org/0000-0002-2715-9930)
- Aleksandra D. Chybowska (ORCID: https://orcid.org/0000-0002-1916-318X)
- Robert F. Hillary (ORCID: https://orcid.org/0000-0002-2595-552X)
- Richard C. Clark (ORCID: https://orcid.org/0000-0002-0066-1541)
- Riccardo E. Marioni (ORCID: https://orcid.org/0000-0003-4430-4260)
- Simon R. Cox (ORCID: https://orcid.org/0000-0003-4036-3642)
- Louise MacGillivray (ORCID: https://orcid.org/0000-0001-7919-2700)
- Elena Bernabeu (ORCID: https://orcid.org/0000-0002-5848-5720)
- Janie Corley (ORCID: https://orcid.org/0000-0002-7551-1871)
- Tara L. Spires‐Jones (ORCID: https://orcid.org/0000-0003-2530-0598)
Institutions
- NHS Lothian (GB)
- Western General Hospital (GB)
- University Hospitals Bristol NHS Foundation Trust (GB)
- Edinburgh Cancer Research (GB)
- University of Bristol (GB)
- UK Dementia Research Institute (GB)
- Medical Research Council (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-04-04
- DOI
- https://doi.org/10.1038/s41467-025-58357-6
- Citations
- 9
- Primary Topic
- Smoking Behavior and Cessation
- Type
- article
- Field-Weighted Citation Impact
- 10.48
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