A blood- and brain-based EWAS of smoking

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

Abstract

Nat Commun. 2025 Apr 4;16(1):3210. doi: 10.1038/s41467-025-58357-6.

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 (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.

PMID:40180905 | DOI:10.1038/s41467-025-58357-6