Yang Sun1, Yanghui Chen2, Yuanyuan Li2, Zongzhe Li1, Chenze Li2, Ting Yu3, Lei Xiao2, Bo Yu2, Hu Zhao3, Min Tao3, Jiangang Jiang1, Jiangtao Yan1, Yan Wang1, Hesong Zeng1, Xiaoqing Shen3, Yiwu Zhou4, Li Jin5, Weihua Song6, Kefei Dou7, Dao Wen Wang8. 1. Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, China. 2. Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, China. 3. Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 4. Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 5. Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China. 6. State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Cardiovascular Institute, Fuwai Hospital and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. 7. State Key Laboratory of Cardiovascular Disease, Department of Cardiology, Cardiovascular Institute, Fuwai Hospital and National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: drdoukefei@126.com. 8. Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, China; Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China. Electronic address: dwwang@tjh.tjmu.edu.cn.
Abstract
BACKGROUND: Spontaneous coronary artery dissection (SCAD) is defined as a splitting of the coronary artery wall exclusive of iatrogenesis or trauma. Since the last decades, our knowledge of the diagnosis and prognosis and therapy for SCAD has advanced; however, its causes remain unknown. OBJECTIVES: This study sought to identify genes associated with SCAD development in the Chinese Han population. METHODS: Between November 2011 and January 2018, the authors enrolled 85 SCAD cases and 296 non-SCAD controls from the Chinese Han population. All 381 subjects enrolled underwent detection with whole exome sequencing, followed by Sanger sequencing for confirmation. Principle component analysis was used to evaluate the structure of the population. Haploview was used to analyze the linkage disequilibrium statistics of the variants. The author used 2 gene-based association tests, optimal sequence kernel association test and mixed effects score test, to identify the causal genes or variants of SCAD. Immunohistochemistry was used to detect the expression of TSR1 in coronary artery tissues. RESULTS: Four genes with a suggestive association with SCAD (p < 5.41 × 10-5 in both the optimal sequence kernel association and mixed effects score tests) were identified, and TSR1 was the top hit. All TSR1 germline variants were either highly conserved across distinct species or lead to premature termination of protein syntheses. Furthermore, the expression of TSR1 was detectable in human coronary artery tissues. CONCLUSIONS: This study describes the clinical characteristics of the Chinese Han population with SCAD and identified TSR1 as a potential causal gene, which might bring about a further progress in diagnosis and treatment of the disorder.
BACKGROUND: Spontaneous coronary artery dissection (SCAD) is defined as a splitting of the coronary artery wall exclusive of iatrogenesis or trauma. Since the last decades, our knowledge of the diagnosis and prognosis and therapy for SCAD has advanced; however, its causes remain unknown. OBJECTIVES: This study sought to identify genes associated with SCAD development in the Chinese Han population. METHODS: Between November 2011 and January 2018, the authors enrolled 85 SCAD cases and 296 non-SCAD controls from the Chinese Han population. All 381 subjects enrolled underwent detection with whole exome sequencing, followed by Sanger sequencing for confirmation. Principle component analysis was used to evaluate the structure of the population. Haploview was used to analyze the linkage disequilibrium statistics of the variants. The author used 2 gene-based association tests, optimal sequence kernel association test and mixed effects score test, to identify the causal genes or variants of SCAD. Immunohistochemistry was used to detect the expression of TSR1 in coronary artery tissues. RESULTS: Four genes with a suggestive association with SCAD (p < 5.41 × 10-5 in both the optimal sequence kernel association and mixed effects score tests) were identified, and TSR1 was the top hit. All TSR1 germline variants were either highly conserved across distinct species or lead to premature termination of protein syntheses. Furthermore, the expression of TSR1 was detectable in human coronary artery tissues. CONCLUSIONS: This study describes the clinical characteristics of the Chinese Han population with SCAD and identified TSR1 as a potential causal gene, which might bring about a further progress in diagnosis and treatment of the disorder.
Authors: Ingrid Tarr; Stephanie Hesselson; Siiri E Iismaa; Emma Rath; Steven Monger; Michael Troup; Ketan Mishra; Claire M Y Wong; Pei-Chen Hsu; Keerat Junday; David T Humphreys; David Adlam; Tom R Webb; Anna A Baranowska-Clarke; Stephen E Hamby; Keren J Carss; Nilesh J Samani; Monique Bax; Lucy McGrath-Cadell; Jason C Kovacic; Sally L Dunwoodie; Diane Fatkin; David W M Muller; Robert M Graham; Eleni Giannoulatou Journal: Circ Genom Precis Med Date: 2022-05-18
Authors: Siiri E Iismaa; Stephanie Hesselson; Lucy McGrath-Cadell; David W Muller; Diane Fatkin; Eleni Giannoulatou; Jason Kovacic; Robert M Graham Journal: Heart Lung Circ Date: 2020-07-06 Impact factor: 2.975
Authors: Carolina Haefliger; David Adlam; Keren J Carss; Anna A Baranowska; Javier Armisen; Tom R Webb; Stephen E Hamby; Diluka Premawardhana; Abtehale Al-Hussaini; Alice Wood; Quanli Wang; Sri V V Deevi; Dimitrios Vitsios; Samuel H Lewis; Deevia Kotecha; Nabila Bouatia-Naji; Stephanie Hesselson; Siiri E Iismaa; Ingrid Tarr; Lucy McGrath-Cadell; David W Muller; Sally L Dunwoodie; Diane Fatkin; Robert M Graham; Eleni Giannoulatou; Nilesh J Samani; Slavé Petrovski Journal: Circ Genom Precis Med Date: 2020-10-30