TY - JOUR
T1 - Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation
AU - CARDIoGRAMplusC4D
AU - MEGASTROKE
AU - International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group
AU - DISCO register
AU - Adlam, David
AU - Berrandou, Takiy Eddine
AU - Georges, Adrien
AU - Nelson, Christopher P.
AU - Giannoulatou, Eleni
AU - Henry, Joséphine
AU - Ma, Lijiang
AU - Blencowe, Montgomery
AU - Turley, Tamiel N.
AU - Yang, Min Lee
AU - Chopade, Sandesh
AU - Finan, Chris
AU - Braund, Peter S.
AU - Sadeg-Sayoud, Ines
AU - Iismaa, Siiri E.
AU - Kosel, Matthew L.
AU - Zhou, Xiang
AU - Hamby, Stephen E.
AU - Cheng, Jenny
AU - Liu, Lu
AU - Tarr, Ingrid
AU - Muller, David W.M.
AU - d’Escamard, Valentina
AU - King, Annette
AU - Brunham, Liam R.
AU - Baranowska-Clarke, Ania A.
AU - Debette, Stéphanie
AU - Amouyel, Philippe
AU - Olin, Jeffrey W.
AU - Patil, Snehal
AU - Hesselson, Stephanie E.
AU - Junday, Keerat
AU - Kanoni, Stavroula
AU - Aragam, Krishna G.
AU - Butterworth, Adam S.
AU - Bakker, Mark K.
AU - Ruigrok, Ynte M.
AU - Tweet, Marysia S.
AU - Gulati, Rajiv
AU - Combaret, Nicolas
AU - Kadian-Dodov, Daniella
AU - Kalman, Jonathan M.
AU - Fatkin, Diane
AU - Hingorani, Aroon D.
AU - Saw, Jacqueline
AU - Webb, Tom R.
AU - Hayes, Sharonne N.
AU - Yang, Xia
AU - Ganesh, Santhi K.
AU - Kovacic, Jason C.
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85160527659&partnerID=8YFLogxK
U2 - 10.1038/s41588-023-01410-1
DO - 10.1038/s41588-023-01410-1
M3 - Article
C2 - 37248441
AN - SCOPUS:85160527659
SN - 1061-4036
VL - 55
SP - 964
EP - 972
JO - Nature Genetics
JF - Nature Genetics
IS - 6
ER -