A blood- and brain-based EWAS of smoking

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 and Riccardo E. Marioni ()
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Aleksandra D. Chybowska: University of Edinburgh
Elena Bernabeu: University of Edinburgh
Paul Yousefi: University of Bristol
Matthew Suderman: University of Bristol
Robert F. Hillary: University of Edinburgh
Richard Clark: Western General Hospital
Louise MacGillivray: Western General Hospital
Lee Murphy: Western General Hospital
Sarah E. Harris: The University of Edinburgh
Janie Corley: The University of Edinburgh
Archie Campbell: University of Edinburgh
Tara L. Spires-Jones: University of Edinburgh
Daniel L. McCartney: University of Edinburgh
Simon R. Cox: The University of Edinburgh
Jackie F. Price: University of Edinburgh
Kathryn L. Evans: University of Edinburgh
Riccardo E. Marioni: University of Edinburgh

Nature Communications, 2025, vol. 16, issue 1, 1-13

Abstract: 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 two British cohorts. Results of brain- and blood-based EWAS (nbrain=14, nblood = 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.

Date: 2025
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DOI: 10.1038/s41467-025-58357-6

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