Mendelian randomization confirms association BMI and cardio-metabolic diseases
Association of Body Mass Index With Cardiometabolic Disease in the UK Biobank
A Mendelian Randomization StudyLiterature - Lyall DM, Celis-Morales C, Ward J, et al. - JAMA Cardiology 2017; published online ahead of print
- In the fully adjusted models of the observational analyses, an SD increase in BMI (4.83 kg/m2) was associated with risk of stroke (OR 1.26, 95% CI 1.21-1.31, P=2.0*10−29), CHD (OR 1.43, 95% CI 1.40-1.46, P=2.0*10−184), type 2 diabetes (OR 1.97, 95% CI 1.93-2.02, P <4.51*10−308), hypertension (OR 1.75, 95% CI 1.73-1.78, P <4.51*10−308), higher SBP (β=3.02 mmHg, 95% CI 2.91-3.13 mmHg, P <4.5*10−308), higher DBP (β=2.82 mmHg, 95% CI 2.76-2.89 mmHg, P <4.5*10−308) and higher pulse rate (β=1.86 beats/min, 95% CI 1.79-1.94 beats/min, P <4.5*10−308).
- The conventional mendelian randomization analyses using individual participant data showed generally similar effect sizes compared with the observational analyses for hypertension (OR 1.64, 95% CI 1.48-1.83, P=1.1*10−19) and CHD (OR 1.35, 95% CI 1.09-1.69, P=0.007). On the other hand, the association with T2DM increased in magnitude compared to the observational OR (mendelian OR 2.53, 95% CI 2.04-3.13). There was no association between BMI and stroke (P=0.93).
- Using MR-Egger, analyses did not identify evidence of unbalanced horizontal pleiotropy. Furthermore, the associations with SBP and DBP remained significant, but pulse rate did not. And results were similar in the partially vs fully adjusted models.
- All findings remained unchanged for T2DM, CHD and hypertension, after removing participants who reported their age at diagnosis as unknown, chose not to answer or had an age ≤10 years at diagnosis as well as after including physical activity in the final models.
In a large population-based cohort study, BMI was associated with risk of hypertension, CHD, T2DM, elevated SBP and DBP based on causal mendelian randomization estimates, but not with stroke or pulse rate. These findings confirm that BMI represents an important modifiable risk factor for decreasing the risk of cardio-metabolic diseases in the general population.