Evidence map›Paper›PMID 42482882›Full record

ArticleTobacco induced diseases2026

Examining the potential causal relationships among smoking, blood DNA methylation, and type 2 diabetes development: A Mendelian randomization study.

Wenhua Li, Yixiao Li, Pan Dong, Jiaxin Tang, Siyang Liu, Ling Tu, Xizhen Xu

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Article in Tobacco induced diseases, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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7 authors.

Wenhua LiDepartment of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Yixiao LiDepartment of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Pan DongDivision of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Jiaxin TangDepartment of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Siyang LiuDepartment of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Ling TuDepartment of Geriatric Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xizhen XuDivision of Cardiology and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionType 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.

methodsWe 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.

resultsIn 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 (

conclusionsThis research provides novel findings of the impact of smoking on T2D susceptibility, highlighting the role of epigenetic DNA methylation.

Indexed as

DNA methylationMendelian randomizationsmokingtype 2 diabetes

Identifiers

PMID42482882
PMCPMC13386699

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