Relationship Between Genetic Prediction of Diabetes and Coronary Atherosclerosis: A Two-Sample Bidirectional Mendelian Randomization Study
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v4i4.1422
Abstract
Background: To explore the relationship between diabetes and coronary atherosclerosis at the genetic level by using two-sample Mendelian randomization (MR). Methods: Diabetes and coronary atherosclerosis are the exposure factors and outcomes respectively. The study employed the inverse-variance weighted method (IVW), MR-Egger regression, weighted median method (WM), simple mode, and weighted mode for bidirectional Mendelian randomization analysis, using the odds ratio (OR) to assess the causal relationship between diabetes and coronary atherosclerosis. Results: MR heterogeneity demonstrated heterogeneity in single nucleotide polymorphisms (SNPs) for each nucleotide (all P values < 0.001). Therefore, the IVW random effects model was selected. The results showed that at the gene level, there was a correlation between an increased risk of diabetes and coronary atherosclerosis (OR=1.103). Additionally, there was a correlation between an increased risk of coronary atherosclerosis and diabetes (OR=1.108). No horizontal pleiotropy of instrumental variables was found (P=0.419, 0.808). The MR analysis results remained robust after sequentially excluding SNPs. Conclusion: Diabetes and coronary atherosclerosis are mutually predisposing risk factors for each other at the gene level in the European population.
Keywords
diabetes, coronary atherosclerosis, mendelian randomization, causal inference
Funding
Key Project of the Guangxi Natural Science Foundation (2023GXNSFDA026008); 2021 Research Project of the Traditional Chinese Medicine Bureau of the Autonomous Region (20210234)
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References
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[1] Liu J, Ren Z H, Qiang H, et al. Trends in the incidence of diabetes mellitus: results from the Global Burden of Disease Study 2017 and implications for diabetes mellitus prevention.[J]. BMC Public Health, 2020,20(1):1415.
[2] Glovaci D, Fan W, Wong N D. Epidemiology of Diabetes Mellitus and Cardiovascular Disease[J]. Curr Cardiol Rep, 2019,21(4):21.
[3] Carnegie R, Zheng J, Sallis H M, et al. Mendelian randomisation for nutritional psychiatry.[Z]. 2020: 7, 208-216.
[4] Hemani G, Zheng J, Elsworth B, et al. The MR-Base platform supports systematic causal inference across the human phenome.[Z]. 2018: 7, null.
[5] Burgess S, Butterworth A, Thompson S G. Mendelian randomization analysis with multiple genetic variants using summarized data.[J]. GENET EPIDEMIOL, 2013,37(7):658-665.
[6] Sekula P, Del Greco M F, Pattaro C, et al. Mendelian Randomization as an Approach to Assess Causality Using Observational Data.[Z]. 2016: 27, 3253-3265.
[7] Burgess S, Bowden J, Fall T, et al. Sensitivity Analyses for Robust Causal Inference from Mendelian Randomization Analyses with Multiple Genetic Variants.[Z]. 2017: 28, 30-42.
[8] Yu TQ, Xu WT, Su YN, et al. Mendelian randomization: the basic principles, methods and limitations[J].Chinese Journal of Evidence-Based Medicine, 2021,21(10):1227-1234.
[9] Iijima R, Ndrepepa G, Kujath V, et al. A pan-coronary artery angiographic study of the association between diabetes mellitus and progression or regression of coronary atherosclerosis.[J]. HEART VESSELS, 2017,32(4):376-384.
[10] Lee C H, Lee S W, Park S W. Diabetes and Subclinical Coronary Atherosclerosis.[Z]. 2018: 42, 355-363.
[11] Park G M, Lee C H, Lee S W, et al. Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis from Coronary Computed Tomographic Angiography Registry.[Z]. 2020: 44, 470-479.
[12] Yahagi K, Kolodgie F D, Lutter C, et al. Pathology of Human Coronary and Carotid Artery Atherosclerosis and Vascular Calcification in Diabetes Mellitus.[Z]. 2017: 37, 191-204.
[13] Wan Z, Fan Y, Liu X, et al. NLRP3 inflammasome promotes diabetes-induced endothelial inflammation and atherosclerosis.[J]. Diabetes Metab Syndr Obes, 2019,12(null):1931-1942.
[14] Colaiori I, Izzo R, Barbato E, et al. Severity of Coronary Atherosclerosis and Risk of Diabetes Mellitus.[J]. J Clin Med, 2019,8(7):null.
[15] Fu Y, Xu L, Zhang H, et al. Identification and Validation of Immune-Related Genes Diagnostic for Progression of Atherosclerosis and Diabetes.[J]. J Inflamm Res, 2023,16(null):505-521.
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