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

By Beate Leppert, Lucy Riglin, Christina Dardani, Ajay Thapar, James R. Staley, Kate Tilling, George Davey Smith, Anita Thapar, Evie Stergiakouli

Posted 10 May 2019
bioRxiv DOI: 10.1101/630467

Objective: Attention-deficit/hyperactivity disorder (ADHD) has been 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 for treatment and prevention but also because comorbid health problems further increase the serious social and economic impacts of ADHD on individuals and their families. Methods: We used a two-sample Mendelian randomization (MR) approach to examine the causal relationships between genetic liability for ADHD and previously implicated physical health conditions. 11 genetic variants associated with ADHD were obtained from the latest summary statistics. Consistent effects obtained from IVW, weighted median and MR Egger methods were taken forward for sensitivity analysis, including bidirectional MR and multivariable MR (MVMR). Results: We 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 but was attenuated when simultaneously controlling for childhood obesity. There was little evidence for a causal effect on other cardiometabolic, immunological, neurological disorders and lung cancer. Conclusion: Our 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 future risk for developing CAD.

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