Evidence mapPaperPMID 39748436Full record

ArticleClinical epigenetics2025

Unraveling the causal impact of smoking and its DNA methylation signatures on cardiovascular disease: Mendelian randomization and colocalization analysis.

Si Cao, Youjie Zeng, Ke Pang, Minghua Chen, Ren Guo, Nayiyuan Wu, Chao Fang, Huiyin Deng, Xiaoyi Zhang, Xiaohui Xie and 2 more

Abstract read
In one paragraph

Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Si Cao *Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Youjie Zeng *Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Ke PangDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Minghua ChenDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Ren GuoDepartment of Pharmacy, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Nayiyuan WuThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.
Chao FangThe Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, Changsha, Hunan, China.
Huiyin DengDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Xiaoyi ZhangDepartment of Medicine, Jacobi Medical Center, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Xiaohui XieDepartment of Medicine, Baylor College of Medicine, Houston, TX, 77030, USA.
Wen OuyangDepartment of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China.
Heng YangDepartment of Neurology, Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, China. johnnelyang@hotmail.com.

Funding

National Natural Science Foundation of Hunan Province 2022JJ70069
6 · The paper itself

Abstract

backgroundTo explore the mechanisms linking smoking to cardiovascular diseases (CVDs) from an epigenetic perspective.

methodsMendelian Randomization (MR) analysis was performed to assess the causal effects of smoking behavior and DNA methylation levels at smoking-related CpG sites on nine CVDs, including aortic aneurysm, atrial fibrillation, coronary atherosclerosis, coronary heart disease, heart failure, intracerebral hemorrhage, ischemic stroke, myocardial infarction, subarachnoid hemorrhage. Colocalization analysis was used to further identify key smoking-related CpG sites from the MR causal estimates. Reactome enrichment analysis was used to elucidate the potential mechanisms.

resultsMR analysis indicates that smoking behaviors are significantly associated with an increased risk of nine CVDs (OR > 1, P < 0.05). Through MR and colocalization analysis, five key smoking-related CpG sites were ultimately determined. DNA methylation alteration at cg25313468 (located in the TSS1500 region of REST) is simultaneously associated with the risk of atrial fibrillation, coronary atherosclerosis, coronary heart disease, and myocardial infarction. Additionally, cg21647257 (located in the TSS200 region of CLIP3) is associated with the risk of atrial fibrillation; cg06197751 (located in SGEF gene body) and cg07520810 (located in ARID5B gene body) are associated with the risk of coronary atherosclerosis; cg16822035 (located in MCF2L gene body) is associated with the risk of myocardial infarction. Enrichment analysis suggests that phosphatase and tensin homologue (PTEN) may be involved in the downstream mechanisms of cg25313468 (REST).

conclusionThis study uncovers the relationship between smoking, DNA methylation, and CVDs, providing new insights into the pathogenic effect of smoking on CVDs from an epigenetic perspective.

Indexed as

Cardiovascular DiseasesCpG IslandsDNA MethylationEpigenesis, GeneticMendelian Randomization AnalysisSmokingHumansCardiovascular diseasesCausal inferenceCigarette smokingDNA methylationMendelian randomizationRisk factors

Identifiers

PMID39748436
PMCPMC11694376

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.