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

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...

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Main Authors: Hua Di, Shouhao Wang, Chengan Xu, Qiaoqiao Yin, Keyang Xu, Wei Zheng
Format: Article
Language:English
Published: Ubiquity Press 2024-11-01
Series:Global Heart
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Online Access:https://account.globalheartjournal.com/index.php/up-j-gh/article/view/1374
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author Hua Di
Shouhao Wang
Chengan Xu
Qiaoqiao Yin
Keyang Xu
Wei Zheng
author_facet Hua Di
Shouhao Wang
Chengan Xu
Qiaoqiao Yin
Keyang Xu
Wei Zheng
author_sort Hua Di
collection DOAJ
description 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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institution Kabale University
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spelling doaj-art-4a6427cc30d24daa8251668caf82a8122024-12-20T07:15:17ZengUbiquity PressGlobal Heart2211-81792024-11-01191888810.5334/gh.13741355Shared Genetic Links Between Nonalcoholic Fatty Liver Disease and Coronary Artery DiseaseHua Di0https://orcid.org/0009-0008-4466-7110Shouhao Wang1https://orcid.org/0000-0001-9947-9629Chengan Xu2https://orcid.org/0000-0003-4761-6518Qiaoqiao Yin3https://orcid.org/0000-0003-2812-0496Keyang Xu4https://orcid.org/0000-0002-7049-2528Wei Zheng5https://orcid.org/0000-0001-6639-2869Geriatric Medicine Center, Department of Acupuncture & Massage, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou 310014, ZhejiangHepatology 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 ProvinceCenter for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014Centre for Cancer & Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong KongCenter for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014Background: 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.https://account.globalheartjournal.com/index.php/up-j-gh/article/view/1374nonalcoholic fatty liver diseasecoronary artery diseasegenetic association studymendelian randomization analysisgenetic pleiotropy
spellingShingle Hua Di
Shouhao Wang
Chengan Xu
Qiaoqiao Yin
Keyang Xu
Wei Zheng
Shared Genetic Links Between Nonalcoholic Fatty Liver Disease and Coronary Artery Disease
Global Heart
nonalcoholic fatty liver disease
coronary artery disease
genetic association study
mendelian randomization analysis
genetic pleiotropy
title Shared Genetic Links Between Nonalcoholic Fatty Liver Disease and Coronary Artery Disease
title_full Shared Genetic Links Between Nonalcoholic Fatty Liver Disease and Coronary Artery Disease
title_fullStr Shared Genetic Links Between Nonalcoholic Fatty Liver Disease and Coronary Artery Disease
title_full_unstemmed Shared Genetic Links Between Nonalcoholic Fatty Liver Disease and Coronary Artery Disease
title_short Shared Genetic Links Between Nonalcoholic Fatty Liver Disease and Coronary Artery Disease
title_sort shared genetic links between nonalcoholic fatty liver disease and coronary artery disease
topic nonalcoholic fatty liver disease
coronary artery disease
genetic association study
mendelian randomization analysis
genetic pleiotropy
url https://account.globalheartjournal.com/index.php/up-j-gh/article/view/1374
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AT qiaoqiaoyin sharedgeneticlinksbetweennonalcoholicfattyliverdiseaseandcoronaryarterydisease
AT keyangxu sharedgeneticlinksbetweennonalcoholicfattyliverdiseaseandcoronaryarterydisease
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