Chybowska Aleksandra D, Bernabeu Elena, Yousefi Paul, Suderman Matthew, Hillary Robert F, Clark Richard, MacGillivray Louise, Murphy Lee, Harris Sarah E, Corley Janie, Campbell Archie, Spires-Jones Tara L, McCartney Daniel L, Cox Simon R, Price Jackie F, Evans Kathryn L, Marioni Riccardo E
Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
Medical Research Council Integrative Epidemiology Unit at the University of Bristol, University of Bristol, Bristol, UK.
Nat Commun. 2025 Apr 4;16(1):3210. doi: 10.1038/s41467-025-58357-6.
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=14, n = 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.
DNA甲基化提供了一种评估吸烟影响的客观方法。在这项工作中，我们对吸烟包年数进行了贝叶斯全基因组关联研究（n = 17865，约85万个位点，Illumina EPIC芯片），并通过分析来自苏格兰世代研究的吸烟者和非吸烟者的全基因组数据（n = 46，通过TWIST和牛津纳米孔测序获得约400 - 2100万个位点）对其进行了扩展。我们开发了mCigarette，一种吸烟的表观遗传生物标志物，并在两个英国队列中对其进行了测试。基于大脑和血液的全基因组关联研究结果（n = 14，n = 882，>45万个位点，Illumina芯片）揭示了几个对吸烟状态具有近乎完美区分能力的基因座，但这些基因座在不同组织之间并不重叠。此外，我们对吸烟的表观遗传进行了全基因组关联研究，确定了几个与吸烟相关的基因座。总体而言，我们通过整合来自多个组织和队列的DNA甲基化数据，提高了与吸烟相关的生物标志物的准确性，并增强了对吸烟影响的理解。
