| Title: | Chromosome 1q21.2 and additional loci influence risk of spontaneous coronary artery dissection and myocardial infarction |
| Journal: | Nature Communications |
| Published: | 4 Sep 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32887874/ |
| DOI: | https://doi.org/10.1038/s41467-020-17558-x |
| URL: | https://www.nature.com/articles/s41467-020-17558-x.pdf |
| Citations: | 66 (31 in last 2 years) as of 8 Aug 2024 |
Publication 4484
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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.</p>
26 Authors
- Jacqueline Saw
- Min-Lee Yang
- Mark Trinder
- Catherine Tcheandjieu
- Chang Xu
- Andrew Starovoytov
- Isabelle Birt
- Michael R. Mathis
- Kristina L. Hunker
- Ellen M. Schmidt
- Linda Jackson
- Natalia Fendrikova-Mahlay
- Matthew Zawistowski
- Chad M. Brummett
- Sebastian Zoellner
- Alexander Katz
- Dawn M. Coleman
- Kirby Swan
- Christopher J. O'Donnell
- Xiang Zhou
- Jun Z. Li
- Heather L. Gornik
- Themistocles L. Assimes
- James C. Stanley
- Liam R. Brunham
- Santhi K. Ganesh
Enabling scientific discoveries that improve human health