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

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...

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Main Authors: Qian Ge, Zhongyan Li, Weijing Meng, Chen Cai, Mengdi Qiu, Yafei Liu, Haibo Zhu
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Brain and Behavior
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Online Access:https://doi.org/10.1002/brb3.70280
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author Qian Ge
Zhongyan Li
Weijing Meng
Chen Cai
Mengdi Qiu
Yafei Liu
Haibo Zhu
author_facet Qian Ge
Zhongyan Li
Weijing Meng
Chen Cai
Mengdi Qiu
Yafei Liu
Haibo Zhu
author_sort Qian Ge
collection DOAJ
description 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.
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spelling doaj-art-6b55d9dae37349bfa5886b1bd3eab3cc2025-01-29T13:36:40ZengWileyBrain and Behavior2162-32792025-01-01151n/an/a10.1002/brb3.70280Assessing the Causal Relationship Between Various Immune Cells and Attention Deficit Hyperactivity Disorder: Mendelian Randomization StudyQian Ge0Zhongyan Li1Weijing Meng2Chen Cai3Mengdi Qiu4Yafei Liu5Haibo Zhu6Huai'an Hospital Affiliated to Yangzhou University, the Fifth People's Hospital of Huai'an Jiangsu ChinaHuai'an Hospital Affiliated to Yangzhou University, the Fifth People's Hospital of Huai'an Jiangsu ChinaHuai'an Hospital Affiliated to Yangzhou University, the Fifth People's Hospital of Huai'an Jiangsu ChinaHuai'an Hospital Affiliated to Yangzhou University, the Fifth People's Hospital of Huai'an Jiangsu ChinaHuai'an Hospital Affiliated to Yangzhou University, the Fifth People's Hospital of Huai'an Jiangsu ChinaHuai'an Hospital Affiliated to Yangzhou University, the Fifth People's Hospital of Huai'an Jiangsu ChinaHuai'an Hospital Affiliated to Yangzhou University, the Fifth People's Hospital of Huai'an Jiangsu ChinaABSTRACT 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.https://doi.org/10.1002/brb3.70280attention deficit hyperactivity disordercausal inferenceimmune cellsMendelian randomizationsensitivity analysis
spellingShingle Qian Ge
Zhongyan Li
Weijing Meng
Chen Cai
Mengdi Qiu
Yafei Liu
Haibo Zhu
Assessing the Causal Relationship Between Various Immune Cells and Attention Deficit Hyperactivity Disorder: Mendelian Randomization Study
Brain and Behavior
attention deficit hyperactivity disorder
causal inference
immune cells
Mendelian randomization
sensitivity analysis
title Assessing the Causal Relationship Between Various Immune Cells and Attention Deficit Hyperactivity Disorder: Mendelian Randomization Study
title_full Assessing the Causal Relationship Between Various Immune Cells and Attention Deficit Hyperactivity Disorder: Mendelian Randomization Study
title_fullStr Assessing the Causal Relationship Between Various Immune Cells and Attention Deficit Hyperactivity Disorder: Mendelian Randomization Study
title_full_unstemmed Assessing the Causal Relationship Between Various Immune Cells and Attention Deficit Hyperactivity Disorder: Mendelian Randomization Study
title_short Assessing the Causal Relationship Between Various Immune Cells and Attention Deficit Hyperactivity Disorder: Mendelian Randomization Study
title_sort assessing the causal relationship between various immune cells and attention deficit hyperactivity disorder mendelian randomization study
topic attention deficit hyperactivity disorder
causal inference
immune cells
Mendelian randomization
sensitivity analysis
url https://doi.org/10.1002/brb3.70280
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