A blood- and brain-based EWAS of smoking.

Chybowska, Aleksandra D; Bernabeu, Elena; Yousefi, Paul; Suderman, Matthew; Hillary, Robert F; Clark, Richard; MacGillivray, Louise; Murphy, Lee et al. · Nat Commun · 2025

basic_science · Level V

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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<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.

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