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Association between Immune Traits and Neurodevelopmental Disorders: A Two-Sample Mendelian Randomization Study
2532 Pages Posted: 22 Dec 2023
More...Abstract
Background: One of the main causes of health-related issues in children is neurodevelopmental disorders (NDDs), which include attention-deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and Tourette syndrome (TS). Nonetheless, there is relatively little prior research looking at the link between immunological inflammation and NDDs. Our work uses a two-sample Mendelian Randomization (MR) approach to provide a thorough evaluation of the causal effects of immune traits on ADHD, ASD, and TS.
Methods: As exposures, 731 immunological traits' genetic associations were chosen, and the outcomes were genome-wide association data for ADHD, ASD, and TS. The inverse-variance weighted (IVW), weighted median (WM), and MR-Egger methods were used to conduct MR analysis. The results' robustness, heterogeneity, and horizontal pleiotropy were confirmed using extensive sensitivity analysis.
Findings: With single-nucleotide polymorphisms serving as instruments and false discovery rate (FDR) correction applied, the study found that significantly higher expression of CD62L on CD62L+ myeloid DC (IVW, OR: 0.926, 95% CI 0.896～0.958, P = 9.42×10–6, FDR = 0.007) and suggestively higher absolute cell count (AC) of CD28+ DN (CD4-CD8-) (IVW, OR: 0.852, 95% CI = 0.780 ~ 0.932, P-value = 4.65 × 10-4, FDR = 0.170) was associated with a lower risk of ADHD. There was no pleiotropy, and the causal relationships were strong according to sensitivity, leave-one-out, and MR-Steiger directionality tests. For ASD and TS, no substantial and suggestive risk immune feature was found.
Interpretations: The results of the study lend credence to the theory that deficiency in CD62L on CD62L+ myeloid DC and CD28+ DN (CD4-CD8) AC may contribute to the onset of ADHD.
Funding: This work was supported by the National Natural Science Foundation of China (No. 82274576) and Traditional Chinese Medicine Inheritance and Development Project of Shanghai Medical Innovation & Development Foundation (No. WLJH2021ZYMZY019).
Declaration of Interest: All authors did not disclose conflicts of interest and all authors' declarations were consistent with those declared in the ICMJE Conflict of Interest Form.
Keywords: Immune trait, Autism spectrum disorder, Attention-deficit hyperactivity disorder, Tourette syndrome, MR analysis, CD62L, CD28
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