Large genetic study of coronary artery disease shows how much we don't know
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We still have a very long way to go
before we understand the genetic underpinnings of coronary artery
disease (CAD), according to the largest and most comprehensive study in
the field performed to date.
In a series of tweets, Sekar Kathiresan, MD, director of preventive cardiology at Massachusetts General Hospital in Boston and co-leader of the study, summarized the meta-analysis of genome-wide association studies, which was published in Nature Genetics:
"Our latest analysis of coronary artery disease genetics is out. 58 DNA variants confer risk. Takeaways from latest CAD genetics study:
The study lends support to the view that further progress in understanding and treating CAD will depend less on lipid research and more on vessel wall biology.
In their paper, the researchers write "a number of preventative strategies target the vessel wall (control of blood pressure and smoking cessation), but the large majority of existing drug treatments for lowering CAD risk operate through manipulation of circulating lipid levels and few directly target vessel wall processes. Detailed investigation of new aspects of vessel wall biology that are implicated by genetic association but have not previously been explored in atherosclerosis may provide new insights into the complex etiology of disease and, hence, identify new targets."
From the American Heart Association:
In a series of tweets, Sekar Kathiresan, MD, director of preventive cardiology at Massachusetts General Hospital in Boston and co-leader of the study, summarized the meta-analysis of genome-wide association studies, which was published in Nature Genetics:
"Our latest analysis of coronary artery disease genetics is out. 58 DNA variants confer risk. Takeaways from latest CAD genetics study:
- Of 58 variants, <20% relate to known risk factors.
- Lots of common variants with weak effects, few low-frequency variants of larger effect.
- Biggest yield = biology @ 80% CAD loci not related to known risk factors -- difficult but nothing worth doing is easy.
- Which risk factors matter most for CAD? Unbiased genetic survey finds only LDL, Lp(a), TG, & SBP."
The study lends support to the view that further progress in understanding and treating CAD will depend less on lipid research and more on vessel wall biology.
In their paper, the researchers write "a number of preventative strategies target the vessel wall (control of blood pressure and smoking cessation), but the large majority of existing drug treatments for lowering CAD risk operate through manipulation of circulating lipid levels and few directly target vessel wall processes. Detailed investigation of new aspects of vessel wall biology that are implicated by genetic association but have not previously been explored in atherosclerosis may provide new insights into the complex etiology of disease and, hence, identify new targets."
From the American Heart Association:
- Basic Concepts and Potential Applications of Genetics and Genomics for Cardiovascular and Stroke Clinicians: A Scientific Statement From the American Heart Association
- Genetics and Genomics for the Prevention and Treatment of Cardiovascular Disease
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