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<p>DNA methylation offers an objective method to assess the impact of smoking. In this work, we conduct a Bayesian EWAS of smoking pack years (<i>n</i> = 17,865, ~850k sites, Illumina EPIC array) and extend it by analysing whole genome data of smokers and non-smokers from Generation Scotland (<i>n</i> = 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, &gt;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.</p>

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A blood- and brain-based EWAS of smoking

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月4日

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  • 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

摘要

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.