Related Experiment Videos
Examining the potential causal relationships among smoking, blood DNA methylation, and type 2 diabetes development: A
Wenhua Li1,2, Yixiao Li1, Pan Dong2
1Department of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Introduction:
Type 2 diabetes (T2D) is a major global health burden with rising prevalence and significant morbidity and mortality. Smoking has been recognized as an independent risk factor for T2D, but the exact underlying mechanisms are not yet fully understood.
Methods:
We conducted a two-sample Mendelian randomization (MR) study to investigate the effects of smoking behaviors and smoking-related DNA methylation on type 2 diabetes (T2D) risk. This secondary analysis was based on publicly available summary statistics. Smoking traits were obtained from a large meta-GWAS of over 1.2 million individuals of European ancestry. DNA methylation data were derived from the CHARGE Consortium EWAS (n=15907) and mQTLs from the GoDMC (n=27750). T2D outcome data were obtained from a European GWAS including 74124 cases and 824006 controls. Replication was performed in FinnGen (17268 cases, 184778 controls) and BioBank Japan (40250 cases, 170615 controls). Stringently selected genetic instruments were applied, and causal effects were estimated primarily using two-sample MR with inverse-variance weighted analysis, complemented by MR-Egger and weighted median approaches, and further validated by colocalization analysis.
Results:
In our genomic analysis, we presented convincing evidence supporting the association between genetically predicted smoking initiation and an increased susceptibility to T2D. In epigenetic analysis, we identified methylation at 21 smoking-related CpG sites associated with T2D risk. Subsequently, 14 of these CpG sites were validated using the FinnGen dataset, and 12 of them were validated using the BBJ dataset. Furthermore, we observed strong colocalization evidence for four CpG sites, including cg23756272 (BCL2), cg03864215 (KCNJ11), cg09861057 (TDRD10) and cg10672416 (C12orf65), and T2D risk.
Conclusions:
This research provides novel findings of the impact of smoking on T2D susceptibility, highlighting the role of epigenetic DNA methylation.
Related Concept Videos
01:26Type II Diabetes I: Introduction
01:22Diabetes Mellitus: Type 2 and Gestational
01:20Pathophysiology of Diabetes
Type 1 diabetes is characterized by autoimmune-mediated destruction of pancreatic β cells, with environmental factors potentially triggering this process in genetically susceptible individuals. Despite many not having a family history, certain genes increase susceptibility, suggesting a...