Chromosome 1q21.2 and additional loci influence risk of spontaneous coronary artery dissection and myocardial infarction - PubMed

Chromosome 1q21.2 and additional loci influence risk of spontaneous coronary artery dissection and myocardial infarction - PubMed

Chromosome 1q21.2 and additional loci influence risk of spontaneous coronary artery dissection and myocardial infarction

Jacqueline Saw 1, Min-Lee Yang 2 3, Mark Trinder 4 5, Catherine Tcheandjieu 6 7 8, Chang Xu 9, Andrew Starovoytov 4, Isabelle Birt 2 3, Michael R Mathis 10, Kristina L Hunker 2 3, Ellen M Schmidt 9, Linda Jackson 5, Natalia Fendrikova-Mahlay 11, Matthew Zawistowski 9, Chad M Brummett 10, Sebastian Zoellner 9, Alexander Katz 2 3 12, Dawn M Coleman 13, Kirby Swan 2 3, Christopher J O'Donnell 14 15, Million Veteran Program; Xiang Zhou 9, Jun Z Li 3, Heather L Gornik 11, Themistocles L Assimes 6 7, James C Stanley 13, Liam R Brunham 4 5, Santhi K Ganesh 16 17

Collaborators, Affiliations 

• PMID: 32887874
 
• DOI: 10.1038/s41467-020-17558-x

Abstract

Spontaneous coronary artery dissection (SCAD) is a non-atherosclerotic cause of myocardial infarction (MI), typically in young women. We undertook a genome-wide association study of SCAD (Ncases = 270/Ncontrols = 5,263) and identified and replicated an association of rs12740679 at chromosome 1q21.2 (Pdiscovery+replication = 2.19 × 10-12, OR = 1.8) influencing ADAMTSL4 expression. Meta-analysis of discovery and replication samples identified associations with P < 5 × 10-8 at chromosome 6p24.1 in PHACTR1, chromosome 12q13.3 in LRP1, and in females-only, at chromosome 21q22.11 near LINC00310. A polygenic risk score for SCAD was associated with (1) higher risk of SCAD in individuals with fibromuscular dysplasia (P = 0.021, OR = 1.82 [95% CI: 1.09-3.02]) and (2) lower risk of atherosclerotic coronary artery disease and MI in the UK Biobank (P = 1.28 × 10-17, HR = 0.91 [95% CI :0.89-0.93], for MI) and Million Veteran Program (P = 9.33 × 10-36, OR = 0.95 [95% CI: 0.94-0.96], for CAD; P = 3.35 × 10-6, OR = 0.96 [95% CI: 0.95-0.98] for MI). Here we report that SCAD-related MI and atherosclerotic MI exist at opposite ends of a genetic risk spectrum, inciting MI with disparate underlying vascular biology.

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