Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors
Abstract Cardiovascular diseases (CVDs) and cerebrovascular diseases (CeVDs) are closely related vascular diseases, sharing common cardiometabolic risk factors (RFs). Although pleiotropic genetic variants of these two diseases have been reported, their underlying pathological mechanisms are still un...
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Nature Portfolio
2024-12-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-024-07417-6 |
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| author | Kexin Ding Xueying Qin Huairong Wang Kun Wang Xiaoying Kang Yao Yu Yang Liu Haiying Gong Tao Wu Dafang Chen Yonghua Hu Tao Wang Yiqun Wu |
| author_facet | Kexin Ding Xueying Qin Huairong Wang Kun Wang Xiaoying Kang Yao Yu Yang Liu Haiying Gong Tao Wu Dafang Chen Yonghua Hu Tao Wang Yiqun Wu |
| author_sort | Kexin Ding |
| collection | DOAJ |
| description | Abstract Cardiovascular diseases (CVDs) and cerebrovascular diseases (CeVDs) are closely related vascular diseases, sharing common cardiometabolic risk factors (RFs). Although pleiotropic genetic variants of these two diseases have been reported, their underlying pathological mechanisms are still unclear. Leveraging GWAS summary data and using genetic correlation, pleiotropic variants identification, and colocalization analyses, we identified 11 colocalized loci for CVDs-CeVDs-BP (blood pressure), CVDs-CeVDs-LIP (lipid traits), and CVDs-CeVDs-cIMT (carotid intima-media thickness) triplets. No shared causal loci were found for CVDs-CeVDs-T2D (type 2 diabetes) or CVDs-CeVDs-BMI (body mass index) triplets. The 11 loci were mapped to 12 genes, namely CASZ1, CDKN1A, TWIST1, CDKN2B, ABO, SWAP70, SH2B3, LRCH1, FES, GOSR2, RPRML, and LDLR, where both GOSR2 and RPRML were mapped to one locus. They were enriched in pathways related to cellular response to external stimulus and regulation of the phosphate metabolic process and were highly expressed in endothelial cells, epithelial cells, and smooth muscle cells. Multi-omics analysis revealed methylation of two genes (CASZ1 and LRCH1) may play a causal role in the genetic pleiotropy. Notably, these pleiotropic loci are highly enriched in the targets of antihypertensive drugs, which further emphasizes the role of the blood pressure regulation pathway in the shared etiology of CVDs and CeVDs. |
| format | Article |
| id | doaj-art-e3900483f98c4825a29994c89ff93ecc |
| institution | DOAJ |
| issn | 2399-3642 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-e3900483f98c4825a29994c89ff93ecc2025-08-20T02:43:25ZengNature PortfolioCommunications Biology2399-36422024-12-017111710.1038/s42003-024-07417-6Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factorsKexin Ding0Xueying Qin1Huairong Wang2Kun Wang3Xiaoying Kang4Yao Yu5Yang Liu6Haiying Gong7Tao Wu8Dafang Chen9Yonghua Hu10Tao Wang11Yiqun Wu12Department of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationDepartment of Medical Epidemiology and Biostatistics, Karolinska InstitutetDepartment of Neurology, Peking University People’s HospitalDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationFangshan District Center for Disease Control and PreventionDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationDepartment of Epidemiology and Population Health, Yeshiva University Albert Einstein College of MedicineDepartment of Epidemiology and Biostatistics, School of Public Health, Peking University; Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of EducationAbstract Cardiovascular diseases (CVDs) and cerebrovascular diseases (CeVDs) are closely related vascular diseases, sharing common cardiometabolic risk factors (RFs). Although pleiotropic genetic variants of these two diseases have been reported, their underlying pathological mechanisms are still unclear. Leveraging GWAS summary data and using genetic correlation, pleiotropic variants identification, and colocalization analyses, we identified 11 colocalized loci for CVDs-CeVDs-BP (blood pressure), CVDs-CeVDs-LIP (lipid traits), and CVDs-CeVDs-cIMT (carotid intima-media thickness) triplets. No shared causal loci were found for CVDs-CeVDs-T2D (type 2 diabetes) or CVDs-CeVDs-BMI (body mass index) triplets. The 11 loci were mapped to 12 genes, namely CASZ1, CDKN1A, TWIST1, CDKN2B, ABO, SWAP70, SH2B3, LRCH1, FES, GOSR2, RPRML, and LDLR, where both GOSR2 and RPRML were mapped to one locus. They were enriched in pathways related to cellular response to external stimulus and regulation of the phosphate metabolic process and were highly expressed in endothelial cells, epithelial cells, and smooth muscle cells. Multi-omics analysis revealed methylation of two genes (CASZ1 and LRCH1) may play a causal role in the genetic pleiotropy. Notably, these pleiotropic loci are highly enriched in the targets of antihypertensive drugs, which further emphasizes the role of the blood pressure regulation pathway in the shared etiology of CVDs and CeVDs.https://doi.org/10.1038/s42003-024-07417-6 |
| spellingShingle | Kexin Ding Xueying Qin Huairong Wang Kun Wang Xiaoying Kang Yao Yu Yang Liu Haiying Gong Tao Wu Dafang Chen Yonghua Hu Tao Wang Yiqun Wu Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors Communications Biology |
| title | Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors |
| title_full | Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors |
| title_fullStr | Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors |
| title_full_unstemmed | Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors |
| title_short | Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors |
| title_sort | identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors |
| url | https://doi.org/10.1038/s42003-024-07417-6 |
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