Exploring the Long-Term Health Consequences of ADHD using a Multivariable Mendelian Randomization Network Approach

Attention-Deficit/Hyperactivity Disorder (ADHD) has been associated with adulthood chronic physical illnesses such as coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). However, the potential causes and mediators which underlie this relationship – such as alcohol use, smoking and educational attainment (EA) –, have not yet been studied simultaneously. This study aimed to investigate the relationship between ADHD, CAD, COPD and these potential causes and mediators by construing a direct causal network using genetic information in a multivariable Mendelian randomization (MR) design. After examining how the individual traits were associated to each other by estimating the genetic (partial) correlations, the total and direct causal effects of the traits on each other were examined using univariable and multivariable MR. The analyses demonstrated evidence for the following direct causal pathway: lower EA increases risk of ADHD diagnosis, causing an increased risk of smoking initiation, causing increased COPD risk. No significant causal relationship between ADHD and CAD could be identified. Future studies should address the reliability and validity of the demonstrated relationships.