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Causality between heart failure and epigenetic age: a bidirectional Mendelian randomization study

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机构: [1]College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, China. [2]Non-Coding RNA and Drug Discovery Key Laboratory of Sichuan Province, Chengdu Medical College, Chengdu, China. [3]School of Basic Medical Sciences, Chengdu Medical College, Chengdu, China. [4]Department of Pediatrics, Shandong Second Provincial General Hospital, Jinan, China. [5]College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. [6]Department of Traditional Chinese Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. [7]Department of Radiation Oncology and Shandong Province Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China. [8]Department of Clinical Pharmacy, Shaoxing People's Hospital, Shaoxing Hospital, Zhejiang University School of Medicine, Shaoxing, China.
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关键词: Epigenetic age Heart failure (HF) Causality Bidirectional Mendelian randomization (MR) study Genome-wide association study (GWAS)

摘要:
Heart failure (HF) is a prevalent age-related cardiovascular disease with poor prognosis in the elderly population. This study aimed to establish the causal relationship between ageing and HF by conducting a bidirectional Mendelian randomization (MR) analysis on epigenetic age (a marker of ageing) and HF.Genome-wide association study data for epigenetic age (GrimAge, HorvathAge, HannumAge, and PhenoAge) and HF were collected and assessed for significant genetic variables. A bidirectional MR analysis was carried out using the random-effects inverse-variance weighted (IVW) method as the primary approach, while other methods (MR-Egger, weighted median, simple mode, and weighted mode) and multiple sensitivity analyses (heterogeneity analysis, leave-one-out sensitivity analysis, and horizontal pleiotropy analysis) were employed to evaluate the impact of epigenetic age on HF and vice versa. Bidirectional MR analysis of two samples revealed that the epigenetic PhenoAge clock increased the risk of HF [IVW odds ratio (OR) 1.015, 95% confidence interval (CI) 1.002-1.028, P = 0.028 and weighted median OR 1.020, 95% CI 1.001-1.038, P = 0.039]. Other results were not statistically significant.The bidirectional MR analysis demonstrated a causal link between genetically predicted epigenetic age and HF in individuals of European descent. Further research into epigenetic age in other populations and additional genetic information related to HF is warranted.© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

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出版当年[2023]版:
大类 | 2 区 医学
小类 | 3 区 心脏和心血管系统
最新[2023]版:
大类 | 2 区 医学
小类 | 3 区 心脏和心血管系统
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第一作者机构: [1]College of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, China.
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