Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation
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Published:2023-05-29
Issue:6
Volume:55
Page:964-972
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ISSN:1061-4036
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Container-title:Nature Genetics
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language:en
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Short-container-title:Nat Genet
Author:
Adlam DavidORCID, Berrandou Takiy-EddineORCID, Georges AdrienORCID, Nelson Christopher P.ORCID, Giannoulatou Eleni, Henry Joséphine, Ma Lijiang, Blencowe Montgomery, Turley Tamiel N., Yang Min-Lee, Chopade Sandesh, Finan ChrisORCID, Braund Peter S.ORCID, Sadeg-Sayoud Ines, Iismaa Siiri E.ORCID, Kosel Matthew L., Zhou XiangORCID, Hamby Stephen E.ORCID, Cheng Jenny, Liu Lu, Tarr Ingrid, Muller David W. M.ORCID, d’Escamard Valentina, King Annette, Brunham Liam R.ORCID, Baranowska-Clarke Ania A., Debette StéphanieORCID, Amouyel PhilippeORCID, Olin Jeffrey W.ORCID, Patil Snehal, Hesselson Stephanie E.ORCID, Junday Keerat, Kanoni StavroulaORCID, Aragam Krishna G.ORCID, Butterworth Adam S.ORCID, Bakker Mark K., Ruigrok Ynte M., Tweet Marysia S., Gulati Rajiv, Combaret NicolasORCID, Kadian-Dodov Daniella, Kalman Jonathan M., Fatkin DianeORCID, Hingorani Aroon D.ORCID, Saw JacquelineORCID, Webb Tom R.ORCID, Hayes Sharonne N.ORCID, Yang XiaORCID, Ganesh Santhi K., Olson Timothy M.ORCID, Kovacic Jason C.ORCID, Graham Robert M.ORCID, Samani Nilesh J., Bouatia-Naji NabilaORCID, , , ,
Abstract
AbstractSpontaneous 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.
Publisher
Springer Science and Business Media LLC
Reference59 articles.
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