Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation,Nature Genetics

当前位置： X-MOL 学术 › Nat. Genet. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation
Nature Genetics ( IF 30.8 ) Pub Date : 2023-05-29 , DOI: 10.1038/s41588-023-01410-1
David Adlam _{1,

2} , Takiy-Eddine Berrandou _{3,

4} , Adrien Georges ₃ , Christopher P Nelson _{1,

2} , Eleni Giannoulatou _{5,

6} , Joséphine Henry ₃ , Lijiang Ma ₇ , Montgomery Blencowe _{8,

9} , Tamiel N Turley ₁₀ , Min-Lee Yang _{11,

12,

13} , Sandesh Chopade _{14,

15} , Chris Finan _{14,

15} , Peter S Braund _{1,

2} , Ines Sadeg-Sayoud ₃ , Siiri E Iismaa _{5,

6} , Matthew L Kosel ₁₆ , Xiang Zhou ₁₇ , Stephen E Hamby _{1,

2} , Jenny Cheng _{8,

9} , Lu Liu ₃ , Ingrid Tarr ₅ , David W M Muller _{5,

6,

18} , Valentina d'Escamard ₁₉ , Annette King ₂₀ , Liam R Brunham ₂₁ , Ania A Baranowska-Clarke _{1,

2} , Stéphanie Debette ₂₂ , Philippe Amouyel ₂₃ , Jeffrey W Olin ₂₀ , Snehal Patil ₁₇ , Stephanie E Hesselson _{5,

6} , Keerat Junday _{5,

6} , Stavroula Kanoni ₂₄ , Krishna G Aragam _{25,

26,

27,

28} , Adam S Butterworth _{29,

30,

31} , , , , Marysia S Tweet ₃₂ , Rajiv Gulati ₃₂ , Nicolas Combaret ₃₃ , , Daniella Kadian-Dodov ₂₀ , Jonathan M Kalman _{34,

35} , Diane Fatkin _{5,

6,

18} , Aroon D Hingorani _{14,

15} , Jacqueline Saw ₃₆ , Tom R Webb _{1,

2} , Sharonne N Hayes ₃₂ , Xia Yang _{8,

9,

37,

38} , Santhi K Ganesh _{11,

13} , Timothy M Olson _{32,

39} , Jason C Kovacic _{5,

6,

18,

19,

20} , Robert M Graham _{5,

6,

18} , Nilesh J Samani _{1,

2} , Nabila Bouatia-Naji ₃

Affiliation

Department of Cardiovascular Sciences, Glenfield Hospital, Leicester, UK.
NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Université Paris Cité, Paris Cardiovascular Research Center, Inserm, Paris, France.
Quantitative Genetics and Genomics, Aarhus University, Aarhus, Denmark.
Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
School of Clinical Medicine, Medicine and Health, University of New South Wales, Sydney, New South Wales, Australia.
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Interdepartmental Program of Molecular, Cellular, and Integrative Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN, USA.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, USA.
Institute for Cardiovascular Science, University College London, London, UK.
British Heart Foundation Research Accelerator, University College London, London, UK.
Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA.
Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Cardiology Department, St Vincent's Hospital, Sydney, New South Wales, Australia.
Cardiovascular Research Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Zena and Michael A. Wiener Cardiovascular Institute and Marie-Josée and Henry R. Kravis Center for Cardiovascular Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Centre for Heart Lung Innovation, Departments of Medicine and Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Neurology, Bordeaux University Hospital, Inserm, Bordeaux, France.
Université de Lille, Inserm, CHU Lille, Institut Pasteur de Lille, RID-AGE - Labex DISTALZ - Risk Factors and Molecular Determinants of Aging-Related Disease, Lille, France.
William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK.
British Heart Foundation Centre of Research Excellence, Division of Cardiovascular Medicine, Addenbrooke's Hospital, Cambridge, UK.
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
Department of Cardiology, CHU Clermont-Ferrand, CNRS, Université Clermont Auvergne, Clermont-Ferrand, France.
Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria, Australia.
Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia.
Vancouver General Hospital, Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada.
Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, Los Angeles, CA, USA.
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, USA.

Spontaneous coronary artery dissection (SCAD) is an understudied cause of myocardial infarction primarily affecting women. It is not known to what extent SCAD is genetically distinct from other cardiovascular diseases, including atherosclerotic coronary artery disease (CAD). Here we present a genome-wide association meta-analysis (1,917 cases and 9,292 controls) identifying 16 risk loci for SCAD. Integrative functional annotations prioritized genes that are likely to be regulated in vascular smooth muscle cells and artery fibroblasts and implicated in extracellular matrix biology. One locus containing the tissue factor gene F3, which is involved in blood coagulation cascade initiation, appears to be specific for SCAD risk. Several associated variants have diametrically opposite associations with CAD, suggesting that shared biological processes contribute to both diseases, but through different mechanisms. We also infer a causal role for high blood pressure in SCAD. Our findings provide novel pathophysiological insights involving arterial integrity and tissue-mediated coagulation in SCAD and set the stage for future specific therapeutics and preventions.

中文翻译：

自发性冠状动脉夹层的全基因组关联荟萃分析确定了与动脉完整性和组织介导的凝血相关的风险变异和基因

自发性冠状动脉夹层（SCAD）是导致女性心肌梗死的一个尚未得到研究的原因。目前尚不清楚 SCAD 在基因上与其他心血管疾病（包括动脉粥样硬化性冠状动脉疾病 (CAD)）有何不同。在此，我们提出了一项全基因组关联荟萃分析（1,917 例病例和 9,292 例对照），确定了 SCAD 的 16 个风险位点。综合功能注释优先考虑可能在血管平滑肌细胞和动脉成纤维细胞中受到调节并与细胞外基质生物学有关的基因。一个含有组织因子基因F3的基因座（参与凝血级联启动）似乎对 SCAD 风险具有特异性。几种相关变异与 CAD 具有截然相反的关联，表明共同的生物过程导致这两种疾病，但通过不同的机制。我们还推断高血压在 SCAD 中具有因果作用。我们的研究结果提供了涉及 SCAD 中动脉完整性和组织介导凝血的新颖病理生理学见解，并为未来的具体治疗和预防奠定了基础。

更新日期：2023-05-30

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南

全部期刊列表>>