RT Journal Article
SR Electronic
T1 Smoking and blood DNA methylation: novel associations, replication of previous findings and assessment of reversibility
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 660878
DO 10.1101/660878
A1 Dugué, Pierre-Antoine
A1 Jung, Chol-Hee
A1 Joo, JiHoon E
A1 Wang, Xiaochuan
A1 Wong, Ee Ming
A1 Makalic, Enes
A1 Schmidt, Daniel F
A1 Baglietto, Laura
A1 Severi, Gianluca
A1 Southey, Melissa C
A1 English, Dallas R
A1 Giles, Graham G
A1 Milne, Roger L
YR 2019
UL http://biorxiv.org/content/early/2019/06/08/660878.abstract
AB We conducted a genome-wide association study of blood DNA methylation and smoking, attempted replication of previously discovered associations, and assessed the reversibility of smoking-associated methylation changes. DNA methylation was measured in baseline peripheral blood samples for 5,044 participants in the Melbourne Collaborative Cohort Study. For 1,032 participants, these measures were repeated using blood samples collected at follow-up, a median of 11 years later. A cross-sectional analysis of the association between smoking and DNA methylation and a longitudinal analysis of changes in smoking status and changes in DNA methylation were conducted. We used our cross-sectional analysis to replicate previously reported associations for current (N=3,327) and former (N=172) smoking. A comprehensive smoking index accounting for the bioactivity of smoking and several aspects of smoking history was constructed to assess the reversibility of smoking-induced methylation changes. We identified 4,496 cross-sectional associations at P<10−7, including 3,296 that were novel. We replicated the majority (90%) of previously reported associations for current and former smokers. In our data, we observed for former smokers a substantial degree of return to the methylation levels of never smokers, compared with current smokers (median: 74%, IQR=63-86%). Consistent with this, we found wide-ranging estimates for the half-life parameter of the comprehensive smoking index. Longitudinal analyses identified 368 sites at which methylation changed upon smoking cessation. Our study provides evidence of many novel associations between smoking and DNA methylation at CpGs across the genome, replicates the vast majority of previously reported associations, and indicates wide-ranging reversibility rates for smoking-induced methylation changes.