OP79 Genetic liability for ADHD and physical health outcomes – a two-sample mendelian randomization study

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of physical health problems, including cardiometabolic, neurological and immunological conditions. Determining whether ADHD plays a causal role in these associations is of great importance not only for early treatment and prevention but also because comorbid health problems further increase the serious social and economic impacts of ADHD on individuals and the society.MethodsWe used a two-sample Mendelian randomization (MR) approach to examine the causal relationships between genetic liability for ADHD and previously implicated physical health conditions. Genetic variants associated with ADHD were obtained from the latest summary statistics for European ancestry from the combined PGC + iPSYCH meta-analysis of ADHD. Consistent effects obtained from IVW, weighted median and MR Egger methods were taken forward for sensitivity analysis. The direction of effect was investigated in a bidirectional MR analysis. Multivariable MR was applied to assess effects of genetic liability for ADHD when adjusted for genetic liability for childhood obesity and lifetime smoking heaviness.ResultsWe found evidence of a causal effect of genetic liability for ADHD on childhood obesity (OR:1.29 (95% CI:1.02,1.63)) and coronary artery disease (CAD) (OR:1.11 (95% CI:1.03,1.19)) with consistent results across different MR approaches. There was further evidence for a bidirectional relationship between genetic liability for ADHD and childhood obesity. The effect of genetic liability for ADHD on CAD was independent of smoking heaviness in a multivariable MR setting (OR:1.14(95% CI:1.08,1.20) but was attenuated when simultaneously entering genetic liability for childhood obesity (OR:1.06 ((95% CI:0.95,1.17)). There was little evidence for a causal effect on other cardiometabolic, immunological, neurological disorders and lung cancer.ConclusionOur findings strengthen the argument for early treatment and support for children with ADHD and their families and especially promoting physical activity and providing them with dietary advice to reduce the future risk for developing CAD.