Genome-wide association meta-analysis of spontaneous coronary artery dissection identifies risk variants and genes related to artery integrity and tissue-mediated coagulation
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- May 29, 2023
- Source ID
- 10.1038/s41588-023-01410-1
Entities
People
- Adam S. Butterworth
- Adrien Georges
- Ania A. Baranowska-clarke
- Annette King
- Aroon Hingorani
- Cardiogramplusc4d
- Chris Finan
- Christopher P Nelson
- Daniella Kadian-dodov
- David Adlam
- David W M Muller
- Diane Fatkin
- Disco Register
- Eleni Giannoulatou
- Ines Sadeg-sayoud
- Ingrid Tarr
- International Stroke Genetics Consortium (isgc) Intracranial Aneurysm Working Group
- Jacqueline Saw
- Jason C. Kovacic
- Jeffrey W. Olin
- Jenny Cheng
- Jonathan M. Kalman
- Joséphine Henry
- Keerat Junday
- Krishna G. Aragam
- Liam R Brunham
- Lijiang Ma
- Lu Liu
- Mark K. Bakker
- Marysia S. Tweet
- Matthew L. Kosel
- Megastroke
- Min-lee Yang
- Montgomery Blencowe
- Nabila Bouatia-Naji
- Nicolas Combaret
- Nilesh J. Samani
- Peter S. Braund
- Philippe Amouyel
- Rajiv Gulati
- Robert M Graham
- Sandesh Chopade
- Santhi K. Ganesh
- Sharonne N. Hayes
- Siiri Iismaa
- Snehal Patil
- Stavroula Kanoni
- Stephanie Debette
- Stephanie Hesselson
- Stephen E Hamby
- Takiy Berrandou
- Tamiel N. Turley
- Timothy M. Olson
- Tom R Webb
- Valentina D’escamard
- Xia Yang
- Xiang Zhou
- Ynte M. Ruigrok