Shared Genetic Links Between Nonalcoholic Fatty Liver Disease and Coronary Artery Disease.

IF 3 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Global Heart Pub Date : 2024-11-26 eCollection Date: 2024-01-01 DOI:10.5334/gh.1374

Hua Di, Shouhao Wang, Chengan Xu, Qiaoqiao Yin, Keyang Xu, Wei Zheng

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引用次数: 0

Abstract

Background: Epidemiological and clinical studies have shown that there is a co-morbidity between nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD).

Methods: In this study, we utilized linkage disequilibrium score regression (LDSC) to evaluate the genetic correlation between non-alcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD). We identified pleiotropic loci and genes using SNP-Level PLACO analysis. Following this, MAGMA gene set enrichment analysis was conducted to assess the biological significance of these pleiotropic genes. Finally, a two-sample two-way Mendelian randomization (MR) analysis was performed to evaluate causal relationships between NAFLD and CAD.

Results: We found a significant genetic correlation between NAFLD and CAD. Secondly, PLACO multi-effect analysis identified 6 sites (mainly involved in the establishment of chylomicrons, mitochondrial membrane protein localization and herpes simplex virus 1 infection signaling pathway). Then, three pleiotropic genes (APOC1, TOMM40 and PBX4) were identified by MAGMA gene analysis. Finally, a two-sample two-way MR analysis suggested that there was no causal relationship between NAFLD and CAD.

Conclusions: Our results show that there are significant gene overlaps and pleiotropic genes between NAFLD and CAD and point out their common molecular mechanisms. These findings provide evidence for the common etiology between them and also help to better understand the pleiotropic nature between NAFLD and CAD, which may be of guiding significance for future treatment strategies.

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非酒精性脂肪肝和冠状动脉疾病之间的共同遗传联系

背景：流行病学和临床研究表明，非酒精性脂肪性肝病（NAFLD）与冠状动脉疾病（CAD）存在合并症。方法：在本研究中，我们利用连锁不平衡评分回归（LDSC）来评估非酒精性脂肪性肝病（NAFLD）和冠状动脉疾病（CAD）之间的遗传相关性。我们使用snp水平PLACO分析鉴定了多效位点和基因。随后，我们进行了MAGMA基因集富集分析，以评估这些多效基因的生物学意义。最后，进行双样本双向孟德尔随机化（MR）分析，以评估NAFLD和CAD之间的因果关系。结果：我们发现NAFLD与冠心病有显著的遗传相关性。其次，PLACO多效应分析鉴定出6个位点（主要涉及乳糜微粒的建立、线粒体膜蛋白定位和单纯疱疹病毒1型感染信号通路）。然后，通过MAGMA基因分析鉴定出3个多效基因（APOC1、TOMM40和PBX4）。最后，两样本双向MR分析表明NAFLD和CAD之间没有因果关系。结论：本研究结果表明NAFLD与CAD之间存在显著的基因重叠和多效性基因，并指出其共同的分子机制。这些发现为两者之间的共同病因提供了证据，也有助于更好地了解NAFLD与CAD之间的多效性，对未来的治疗策略具有指导意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Global Heart Medicine-Cardiology and Cardiovascular Medicine

CiteScore

5.70

自引率

5.40%

发文量

审稿时长

5 weeks

期刊介绍： Global Heart offers a forum for dialogue and education on research, developments, trends, solutions and public health programs related to the prevention and control of cardiovascular diseases (CVDs) worldwide, with a special focus on low- and middle-income countries (LMICs). Manuscripts should address not only the extent or epidemiology of the problem, but also describe interventions to effectively control and prevent CVDs and the underlying factors. The emphasis should be on approaches applicable in settings with limited resources. Economic evaluations of successful interventions are particularly welcome. We will also consider negative findings if important. While reports of hospital or clinic-based treatments are not excluded, particularly if they have broad implications for cost-effective disease control or prevention, we give priority to papers addressing community-based activities. We encourage submissions on cardiovascular surveillance and health policies, professional education, ethical issues and technological innovations related to prevention. Global Heart is particularly interested in publishing data from updated national or regional demographic health surveys, World Health Organization or Global Burden of Disease data, large clinical disease databases or registries. Systematic reviews or meta-analyses on globally relevant topics are welcome. We will also consider clinical research that has special relevance to LMICs, e.g. using validated instruments to assess health-related quality-of-life in patients from LMICs, innovative diagnostic-therapeutic applications, real-world effectiveness clinical trials, research methods (innovative methodologic papers, with emphasis on low-cost research methods or novel application of methods in low resource settings), and papers pertaining to cardiovascular health promotion and policy (quantitative evaluation of health programs.