1. Genetically modulated educational attainment and coronary disease risk
- Author
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Lingyao Zeng, Thorsten Kessler, Jeanette Erdmann, Ioanna Ntalla, Panos Deloukas, John Danesh, Hugh Watkins, Heribert Schunkert, Adnan Kastrati, Nilesh J. Samani, Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository
- Subjects
Male ,Coronary Disease ,Genome-wide association study ,030204 cardiovascular system & hematology ,Coronary artery disease ,Genome-wide association studies ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,0302 clinical medicine ,Basic Science ,Risk Factors ,Mendelian randomization ,Genetics ,Genetic predisposition ,Humans ,Medicine ,Genetic Predisposition to Disease ,Life Style ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,business.industry ,School education ,Genetic Variation ,Mendelian Randomization Analysis ,Odds ratio ,Atherosclerosis ,Confidence interval ,Educational attainment ,3. Good health ,Educational Status ,Female ,Cardiology and Cardiovascular Medicine ,business ,Body mass index ,Genome-Wide Association Study ,Demography - Abstract
Aims Genetic disposition and lifestyle factors are understood as independent components underlying the risk of multiple diseases. In this study, we aim to investigate the interplay between genetics, educational attainment—an important denominator of lifestyle—and coronary artery disease (CAD) risk. Methods and results Based on the effect sizes of 74 genetic variants associated with educational attainment, we calculated a ‘genetic education score’ in 13 080 cases and 14 471 controls and observed an inverse correlation between the score and risk of CAD [P = 1.52 × 10−8; odds ratio (OR) 0.79, 95% confidence interval (CI) 0.73–0.85 for the higher compared with the lowest score quintile]. We replicated in 146 514 individuals from UK Biobank (P = 1.85 × 10−6) and also found strong associations between the ‘genetic education score’ with ‘modifiable’ risk factors including smoking (P = 5.36 × 10−23), body mass index (BMI) (P = 1.66 × 10−30), and hypertension (P = 3.86 × 10−8). Interestingly, these associations were only modestly attenuated by adjustment for years spent in school. In contrast, a model adjusting for BMI and smoking abolished the association signal between the ‘genetic education score’ and CAD risk suggesting an intermediary role of these two risk factors. Mendelian randomization analyses performed with summary statistics from large genome-wide meta-analyses and sensitivity analysis using 1271 variants affecting educational attainment (OR 0.68 for the higher compared with the lowest score quintile; 95% CI 0.63–0.74; P = 3.99 × 10−21) further strengthened these findings. Conclusion Genetic variants known to affect educational attainment may have implications for a health-conscious lifestyle later in life and subsequently affect the risk of CAD.
- Published
- 2019