Fig. 1

Study design. Epigenome-wide and transcriptome-wide association studies were performed in 345 adipose tissue samples, identifying 42 smoking-DMS and 42 smoking-DES where five genes (14 CpG sites) overlapped. The 42 smoking-DMS were replicated in 104 independent subjects from the LEAP cohort, and the 14 smoking-DMS were further explored in blood, skin, and lung tissue for tissue-shared effects. DNA methylation and gene expression profiles at the 42 smoking-DMS and 42 smoking-DES were tested for smoking cessation reversibility in 197 ex-smokers. Heritability and QTL analyses testing genetic and environmental influences on methylation in the 542 adipose samples were also carried out. The final set of analyses focused on exploring the link between the 42 smoking-DMS and 42 smoking-DES with metabolic phenotypes. Phenotype associations with smoking-DMS were replicated in 69 Finnish twins. The last set of analyses explored the potential of methylation and gene expression levels at smoking-DMS and smoking-DES to predict future long-term changes in adiposity phenotypes in individuals who go on to quit smoking