Causal relationship between attention deficit hyperactivity disorder and atherosclerosis: A bidirectional Mendelian randomization study

Abstract

Employing a bidirectional 2-sample Mendelian Randomization (MR) approach, this study endeavors to assess the potential causal relationship between attention deficit hyperactivity disorder (ADHD) and atherosclerosis (AS). Single nucleotide polymorphism loci, associated with ADHD at a significant threshold (P < 5 × 10-8), were meticulously screened from genome-wide association studies datasets to serve as instrumental variables. The primary outcomes under investigation encompass AS, coronary atherosclerosis, and cerebral atherosclerosis. Employing inverse variance weighted method (IVW), MR-Egger regression, weighted median method, simple mode and weighted mode, MR analyses were executed to systematically evaluate the causal relationships between ADHD and AS, coronary atherosclerosis, and cerebral atherosclerosis. The MR analysis reveals a positive and statistically significant causal relationship between ADHD and AS (OR = 1.167, 95% CI = 1.003-1.359, P = .046). Notably, no discernible causal links were identified between ADHD and coronary atherosclerosis or cerebral atherosclerosis. Furthermore, there is a lack of evidence supporting an augmented risk of AS, coronary atherosclerosis, or cerebral atherosclerosis associated with ADHD. Through MR analysis, it was found that ADHD increases the risk of AS. However, no causal association has been identified in studies and reverse studies investigating the relationship between ADHD and both coronary atherosclerosis and cerebral atherosclerosis. Therefore, while ADHD may elevate the susceptibility to AS, further investigations are warranted to clarify the exact nature of this association.

Keywords: Mendelian randomization; atherosclerosis; attention deficit hyperactivity disorder; causal association.