Genetic and Lifestyle Risks for CVD and Diabetes

Study Questions:

What is the influence of combined health behaviors and factors within genetic risk groups for developing coronary artery disease (CAD), atrial fibrillation (AF), stroke, hypertension, and type 2 diabetes, and is there interaction between genetic risk and lifestyle?


A total of 339,003 unrelated individuals of white British descent with available genetic data were included in this study from the UK Biobank population-based sample. Individuals were included in the analyses of one or more new-onset diseases. Data were analyzed from April 2006 to March 2015. Polygenic risk scores were created following an additive model for CAD, AF, stroke, hypertension, and diabetes separately. Genetic risk was categorized as low (quintile 1), intermediate (quintiles 2-4), or high (quintile 5). Within each genetic risk group, the risks of incident events were associated with ideal (≥3 ideal lifestyle factors), poor (≥3 poor ideal lifestyle factors), and intermediate (all other combinations). The combined health behaviors and factors were investigated and compared with low genetic risk and ideal lifestyle. Validated tools were used for defining health behaviors for smoking, body mass index, physical activity, and diet. The study used self-reported diagnosis, medication, and hospital episodes.


Of 339,003 individuals, 181,702 (53.6%) were female, and the mean (standard deviation) age was 56.86 (7.99) years. During follow-up, 3.0% developed CAD, 2.1% developed AF, 0.9% developed a stroke, 4.8% developed hypertension, and 1.4% developed diabetes. Genetic risk and lifestyle were independent predictors of incident events, and there were no interactions for any outcome. Compared with ideal lifestyle in the low genetic risk group, poor lifestyle in the high genetic risk group was associated with a hazard ratio of up to 4.54 (95% confidence interval [CI], 3.72-5.54) for CAD, 5.41 (95% CI, 4.29-6.81) for AF, 4.68 (95% CI, 3.85-5.69) for hypertension, 2.26 (95% CI, 1.63-3.14) for stroke, and 15.46 (95% CI, 10.82-22.08) for diabetes.


Genetic composition and combined health behaviors and factors had a log-additive effect on the risk of developing cardiovascular disease. The relative effects of poor lifestyle were comparable between genetic risk groups. Behavioral lifestyle changes should be encouraged for all through comprehensive, multifactorial approaches, although high-risk individuals may be selected based on the genetic risk.


To what degree the genetic risk score, the American College of Cardiology/American Heart Association 10-year risk score, the Reynolds Risk Score, the coronary calcium score, or other biomarkers affect lifelong compliance with recommended lifestyle modification remains to be seen.

Clinical Topics: Arrhythmias and Clinical EP, Diabetes and Cardiometabolic Disease, Prevention, Atherosclerotic Disease (CAD/PAD), Genetic Arrhythmic Conditions, Atrial Fibrillation/Supraventricular Arrhythmias, Diet, Exercise, Hypertension, Smoking

Keywords: Atrial Fibrillation, Biological Specimen Banks, Body Mass Index, Coronary Artery Disease, Diabetes Mellitus, Type 2, Diet, Exercise, Genetics, Hypertension, Life Style, Primary Prevention, Risk Factors, Smoking, Stroke

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