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; Riccardo E. Marioni

doi:10.1038/s41467-025-58357-6

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, Riccardo E. Marioni^*

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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.

Original language	English
Article number	3210
Number of pages	13
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-58357-6
Publication status	Published - 4 Apr 2025

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© The Author(s) 2025.

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8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival
Martin, R. M. (Principal Investigator)
1/10/20 → 30/09/25
Project: Research

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Chybowska, A. D., Bernabeu, E., Yousefi, P., Suderman, M., Hillary, R. F., Clark, R., MacGillivray, L., Murphy, L., Harris, S. E., Corley, J., Campbell, A., Spires-Jones, T. L., McCartney, D. L., Cox, S. R., Price, J. F., Evans, K. L., & Marioni, R. E. (2025). A blood- and brain-based EWAS of smoking. Nature Communications, 16(1), Article 3210. https://doi.org/10.1038/s41467-025-58357-6

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title = "A blood- and brain-based EWAS of smoking",

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.",

author = "Chybowska, {Aleksandra D.} and Elena Bernabeu and Paul Yousefi and Matthew Suderman and Hillary, {Robert F.} and Richard Clark and Louise MacGillivray and Lee Murphy and Harris, {Sarah E.} and Janie Corley and Archie Campbell and Spires-Jones, {Tara L.} and McCartney, {Daniel L.} and Cox, {Simon R.} and Price, {Jackie F.} and Evans, {Kathryn L.} and Marioni, {Riccardo E.}",

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AU - Chybowska, Aleksandra D.

AU - Bernabeu, Elena

AU - Yousefi, Paul

AU - Suderman, Matthew

AU - Hillary, Robert F.

AU - Clark, Richard

AU - MacGillivray, Louise

AU - Murphy, Lee

AU - Harris, Sarah E.

AU - Corley, Janie

AU - Campbell, Archie

AU - Spires-Jones, Tara L.

AU - McCartney, Daniel L.

AU - Cox, Simon R.

AU - Price, Jackie F.

AU - Evans, Kathryn L.

AU - Marioni, Riccardo E.

PY - 2025/4/4

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AB - 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.

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JO - Nature Communications

JF - Nature Communications

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ER -

A blood- and brain-based EWAS of smoking

Abstract

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Projects

8074 (C18281/A29019) ICEP2 - Programme Award: Towards improved casual evidence and enhanced prediction of cancer risk and survival

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