Adlam, David and Berrandou, Takiy-Eddine and Georges, Adrien and Nelson, Christopher P. and Giannoulatou, Eleni and Henry, Joséphine and Ma, Lijiang and Blencowe, Montgomery and Turley, Tamiel N. and Yang, Min-Lee and Chopade, Sandesh and Finan, Chris and Braund, Peter S. and Sadeg-Sayoud, Ines and Iismaa, Siiri E. and Kosel, Matthew L. and Zhou, Xiang and Hamby, Stephen E. and Cheng, Jenny and Liu, Lu and Tarr, Ingrid and Muller, David W. M. and d’Escamard, Valentina and King, Annette and Brunham, Liam R. and Baranowska-Clarke, Ania A. and Debette, Stéphanie and Amouyel, Philippe and Olin, Jeffrey W. and Patil, Snehal and Hesselson, Stephanie E. and Junday, Keerat and Kanoni, Stavroula and Aragam, Krishna G. and Butterworth, Adam S. and Bakker, Mark K. and Ruigrok, Ynte M. and Tweet, Marysia S. and Gulati, Rajiv and Combaret, Nicolas and Kadian-Dodov, Daniella and Kalman, Jonathan M. and Fatkin, Diane and Hingorani, Aroon D. and Saw, Jacqueline and Webb, Tom R. and Hayes, Sharonne N. and Yang, Xia and Ganesh, Santhi K. and Olson, Timothy M. and Kovacic, Jason C. and Graham, Robert M. and Samani, Nilesh J. and Bouatia-Naji, Nabila (2023) 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, 55 (6). pp.964-972. ISSN 1061-4036
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Abstract
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.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 10 Jul 2023 03:39 |
| Last Modified: | 10 Jul 2023 04:48 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1406 |
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