Identification of Immune Traits Associated with Neurodevelopmental Disorders by Two-sample Mendelian Randomization Analysis

Overview

Journal BMC Psychiatry

Publisher Biomed Central

Specialty Psychiatry

Date 2024 Oct 25

PMID 39448971

Authors

Jing Chen

Zhaopeng Han

Zhuiyue Wang

Lifei Chen

Shuxia Wang

Wenbo Yao

Zheng Xue

Affiliations

Soon will be listed here.

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.

Results: 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, 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, 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 harmful or protective immune traits were observed.

Conclusions: 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.

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