Attention-deficit/hyperactivity disorder and ischemic stroke: A Mendelian randomization study.

Area of Science:

• Neuroscience
• Genetics
• Cardiovascular Medicine

Background:

• Observational studies suggest a link between attention-deficit/hyperactivity disorder (ADHD) and ischemic stroke.
• Understanding the causal relationship is crucial for effective prevention and treatment strategies.

Purpose of the Study:

• To investigate the causal effect of genetic liability to ADHD on ischemic stroke and its subtypes.
• To explore potential mediating factors in the ADHD-stroke association.

Main Methods:

• Two-sample Mendelian randomization (MR) study utilizing genetic variants associated with ADHD.
• Outcome data from the MEGASTROKE consortium for ischemic stroke and its subtypes.
• Sensitivity analyses and multivariable MR (MVMR) were employed to ensure robustness and explore mediation.

Main Results:

• Genetic liability to ADHD was significantly associated with an increased risk of any ischemic stroke (AIS) (OR=1.15, P=0.002).
• A stronger association was observed for large-artery atherosclerotic stroke (LAS) (OR=1.40, P=0.005).
• Sensitivity and MVMR analyses confirmed these findings and indicated mediation by coronary artery disease.

Conclusions:

• Genetic predisposition to ADHD causally increases the risk of ischemic stroke, especially LAS.
• The association between ADHD and LAS is independent of smoking initiation age but is mediated by coronary artery disease.