Di Hua, Wang Shouhao, Xu Chengan, Yin Qiaoqiao, Xu Keyang, Zheng Wei
Geriatric Medicine Center, Department of Acupuncture & Massage, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.
Hepatology Diagnosis and Treatment Center, The First Affiliated Hospital of Wenzhou Medical University and Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou 325035, Zhejiang Province, China.
Glob Heart. 2024 Nov 26;19(1):88. doi: 10.5334/gh.1374. eCollection 2024.
Epidemiological and clinical studies have shown that there is a co-morbidity between nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD).
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.
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.
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.
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）之间存在共病现象。
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）与冠状动脉疾病（CAD）之间的遗传相关性。我们使用单核苷酸多态性水平的多效性分析（SNP-Level PLACO分析）来识别多效性位点和基因。在此之后，进行基因集变异分析（MAGMA）以评估这些多效性基因的生物学意义。最后，进行两样本双向孟德尔随机化（MR）分析以评估NAFLD与CAD之间的因果关系。
我们发现NAFLD与CAD之间存在显著的遗传相关性。其次，PLACO多效应分析确定了6个位点（主要涉及乳糜微粒的形成、线粒体膜蛋白定位和单纯疱疹病毒1感染信号通路）。然后，通过MAGMA基因分析确定了三个多效性基因（载脂蛋白C1、转运蛋白40和预B细胞白血病转录因子4）。最后，两样本双向MR分析表明NAFLD与CAD之间不存在因果关系。
我们的结果表明，NAFLD与CAD之间存在显著的基因重叠和多效性基因，并指出了它们共同的分子机制。这些发现为它们之间的共同病因提供了证据，也有助于更好地理解NAFLD与CAD之间的多效性本质，这可能对未来的治疗策略具有指导意义。
