Waterpipe and cigarette epigenome analysis reveals markers implicated in addiction and smoking type inference

Zainab Awada; Vincent Cahais; Cyrille Cuenin; Reem Akika; Anna Luiza Silva Almeida Vicente; Maha Makki; Hani Tamim; Zdenko Herceg; Nathalie Khoueiry Zgheib; Akram Ghantous

doi:10.1016/j.envint.2023.108260

Waterpipe and cigarette epigenome analysis reveals markers implicated in addiction and smoking type inference

Environ Int. 2023 Dec:182:108260. doi: 10.1016/j.envint.2023.108260. Epub 2023 Oct 18.

Authors

Affiliations

¹ Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France.
² Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
³ Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France; Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
⁴ Clinical Research Institute, American University of Beirut Medical Center, Beirut, Lebanon.
⁵ Clinical Research Institute, American University of Beirut Medical Center, Beirut, Lebanon; College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
⁶ Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. Electronic address: nk16@aub.edu.lb.
⁷ Epigenomics and Mechanisms Branch, International Agency for Research on Cancer, Lyon, France. Electronic address: GhantousA@iarc.who.int.

Abstract

Waterpipe smoking is frequent in the Middle East and Africa with emerging prevalence worldwide. The epigenome acts as a molecular sensor to exposures and a crucial driver in several diseases. With the widespread use of waterpipe smoking, it is timely to investigate its epigenomic markers and their role in addiction, as a central player in disease prevention and therapeutic strategies. DNA methylome-wide profiling was performed on an exposure-rich population from the Middle East, constituting of 216 blood samples split equally between never, cigarette-only and waterpipe-only smokers. Waterpipe smokers showed predominantly distinct epigenetic markers from cigarette smokers, even though both smoking forms are tobacco-based. Moreover, each smoking form could be accurately (∼90 %) inferred from the DNA methylome using machine learning. Top markers showed dose-response relationship with extent of smoking and were validated using independent technologies and additional samples (total N = 284). Smoking markers were enriched in regulatory regions and several biological pathways, primarily addiction. The epigenetically altered genes were not associated with genetic etiology of tobacco use, and the methylation levels of addiction genes, in particular, were more likely to reverse after smoking cessation. In contrast, other epigenetic markers continued to feature smoking exposure after cessation, which may explain long-term health effects observed in former smokers. This study reports, for the first time, blood epigenome-wide markers of waterpipe smokers and reveals new markers of cigarette smoking, with implications in mechanisms of addiction and the capacity to discriminate between different smoking types. These markers may offer actionable targets to reverse the epigenetic memory of addiction and can guide future prevention strategies for tobacco smoking as the most preventable cause of illnesses worldwide.

Keywords: Addiction; Biomarker; Cigarette; DNA methylation; Smoking inference; Waterpipe.

MeSH terms

Cigarette Smoking* / genetics
Epigenome*
Humans
Middle East / epidemiology
Tobacco Products*
Water Pipe Smoking* / genetics

Grants and funding

001/WHO_/World Health Organization/International