personalized cardiovascular medicine and genomics · personalized cardiovascular medicine and...
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Personalized Cardiovascular Medicine and Genomics
Shaista Malik, MD, PhD, MPH Associate Professor of Medicine
Medical Director, Preventive Cardiology and Cardiac Rehab Executive Director, Susan Samueli Integrative Health Institute
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Disclosures
• None • Grant Funding
• NIH/NHLBI R01HL128801 • NIH/NCCIH R01AT009247 • NIH/NHLBI R01HL072125
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A SNP is a single-letter change in DNA, part of the natural genetic variation (at least 1%) within a population. Human genome has 3 billion nucleotides. 500,000 SNP provide, on average, a marker every 6,000 nucleotides. Image courtesy of Lauren Solomon, the Broad Institute
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Genome Wide Association Studies (GWAS): SNPs common and occuring on average in 50% of the population.
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Genome Wide Association Studies (GWAS): SNPs and CVD risk factor associations
Most SNPs do not code for protein. this means the risk variant mediates its increased risk for CVD directly or indirectly through regulation of DNA sequences that do code for proteins
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Weights are generally assigned to each genetic variant according to the strength of their association with disease risk (effect estimate). Individuals are scored based on how many risk alleles they have for each variant (for example, zero, one, or two copies) included in the polygenic score
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Nature Genetics, 2018 Area Under Curve (AUC) measures discrimination, that is, the ability of the test to correctly classify those with and without the disease.
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Polygenic risk and CAD
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Genetics and Lifestyle
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Healthy Lifestyle: no smoking, no obesity, physical activity at least once weekly, and a healthy diet pattern. At least half of the following: Increased: • fruits, vegetables, • Nuts • Whole grains, • fish, • dairy products Reduced • refined grains, • processed meats, unprocessed red meats, • sugar-sweetened beverages, • trans fats • sodium
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PLOS Genetics July 2013
Occupational physical activity in most studies was categorized as i) sedentary or standing; ii) light but partly physically active; iii) light and physically active; and iv) sometimes or often physically straining. Leisure time physical activity during the past three months was categorized as exercising: i) occasionally; ii) 1–2 times/week; iii) 2–3 times/week; or iv) 3 times/week
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Lancet, 2015
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APOA2 SNP rs
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Use of ApoE Polymorphism in Guiding Dietary Choices
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Use of ApoE Polymorphism in Guiding Dietary Choices
J Cell Mol Med. 2008, 12(6b): 2762-2771
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Conclusion
• Genetic Risk Scoring can have good discrimination • Understanding pathways will be key • Need to be tested for clinical utility