Cardio metabolic traits and lung function: A Mendelian Randomization study

<b>Background:</b> Observational studies show that lung function is associated with cardio metabolic traits (e.g. BMI, coronary artery disease, type 2 diabetes, blood pressure) and markers of systemic inflammation (e.g. CRP). However, these associations may be confounded by shared risk factors (e.g. smoking). In this study we investigated whether the associations of lung function with cardio metabolic traits may be causal. <b>Methods:</b> We selected instrumental variables from published large scale genome-wide association studies, including SNPs with P&lt; 5x10-8. SNPs were selected for BMI (Locke et al. 2015), for CAD (Nikpay et al. 2015), for T2D (Scott et al 2017), for CRP (Dehghan et al. 2011), for systolic (SBP) and diastolic blood pressure (summary statistics, UK Biobank). We calculated MR estimates using an inverse-variance weighted method. We used the selected instruments as risk factors, and lung function measures (FEV1, FVC, FEV1/FVC) as an outcome, using data from 275899 individuals in the UK Biobank. <b>Results:</b> MR estimates suggest a negative association of BMI with FEV1 and FVC and a positive association with FEV1/FVC (P&lt; 4.1x10-12). T2D showed a negative association of FEV1 and FVC1 (P&lt;3.3x10-9). SBP was negatively associated with FEV1, FVC and FEV1/FVC (P&lt; 5.1x10-6) as were also CRP with FEV1 and FVC (P&lt;6.3x10-4). We did not find significant associations between CAD and lung function. <b>Conclusion:</b> We show, by using genetic instruments, that the observational associations of BMI, T2D, SBP, CRP and lung function are unlikely to be confounded and may be causal. Investigation of possible pleiotropic effects are currently being performed to further explore these findings. <b>Funding:</b> EU H2020 grant 633212