Assessing the Causal Relationship Between Various Immune Cells and Attention Deficit Hyperactivity Disorder: Mendelian Randomization Study

Abstract

ABSTRACT Background Immune system modulation has been shown to have a significant impact on attention deficit hyperactivity disorder (ADHD). Mendelian randomization (MR) analysis was used in this study to investigate the potential role of different immune cells in the development of ADHD to provide therapy and preventative alternatives. Methods In this study, 731 immune cells and the risk of ADHD were examined using publicly accessible genetic data and a two‐sample MR analysis. Included were four different types of immunological profiles: determinate cells (DC), proportional cells (PC), median brightness level (MBL), and morphological characteristics (MA). It was discovered that single‐nucleotide polymorphisms (SNPs) are linked to ADHD. To evaluate the dependability of the results, we conducted sensitivity analysis (heterogeneity and pleiotropy) and employed supplementary MR techniques, such as the inverse variance weighted (IVW) and MR‐Egger. Graphs are used to display the final findings of the pertinent analyses. Results Following MR analysis, immune cells associated with a few low p value phenotypes may influence ADHD, and these immune cells may serve as an inspiration for clinical treatment practices that aim to prevent and cure ADHD. Immune cell phenotypes that may both increase and worsen the likelihood of having ADHD were identified by IVW results. These included CD27 on memory B cells (OR = 1.066, 95% CI = 1.024–1.109, p = 2E−3) and CD27 on IgD−CD38− (OR = 1.059, 95% CI = 1.018–1.103, p = 5E−3), among others. Immune cell phenotypes that may act as a safeguard against ADHD included CD3 on resting Treg (OR = 0.925, 95% CI = 0.888–0.963, p = 1.5E−4) and SSC‐A on monocytes (OR = 0.951, 95% CI = 0.924–0.980, p = 8.5E−4), among others. The primary findings and the outcomes of the sensitivity analysis matched. Conclusions This study provides a broad theoretical foundation for the development of immune‐oriented therapeutic strategies in future clinical practice by demonstrating a potential genetic relationship between immune cells and ADHD. This study also advances our understanding of how to use the immune pathway to prevent and treat ADHD.

Keywords

• attention deficit hyperactivity disorder
• causal inference
• immune cells
• Mendelian randomization
• sensitivity analysis