ADHD genetic liability and physical health outcomes - A two-sample Mendelian randomization study

Attention-deficit/hyperactivity disorder (ADHD) is associated with a broad range of physical health problems. Using different research designs to test whether ADHD has a causal role in these associations is of great importance because comorbid health problems further increase the serious social and economic impacts of ADHD. We used two-sample Mendelian randomization (MR) to infer causal relationships between ADHD, indexed by genetic instrumental variables, and previously implicated physical health conditions. Different MR methods were used to test the robustness and plausibility of our findings. Consistent findings were taken forward for bidirectional and multivariable MR. There was little evidence for inferring a causal effect on other cardiometabolic, autoimmune, allergic and neurological diseases. We found evidence in favor of ADHD having a causal effect 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 MR approaches. There was further MR evidence for a bidirectional relationship between ADHD and childhood obesity. The relationship with CAD attenuated when controlling for childhood obesity. Our findings strengthen the argument for effective treatment of children with ADHD. It also suggests that clinicians who manage ADHD need to be aware of the risk of childhood obesity to reduce future risks of CAD.