Dataset Information

Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization analysis.

ABSTRACT:

Background

Childhood neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS), comprise a major cause of health-related disabilities in children. However, biomarkers towards pathogenesis or novel drug targets are still limited. Our study aims to provide a comprehensive investigation of the causal effects of the plasma proteome on ASD, ADHD, and TS using the two-sample Mendelian Randomization (MR) approach.

Methods

Genetic associations with 2994 plasma proteins were selected as exposures and genome-wide association data of ASD, ADHD, TS were utilized as outcomes. MR analyses were carried out using the inverse-variance weighted method, and the MR-Egger and weighted median methods were used for sensitivity analysis.

Findings

Using single-nucleotide polymorphisms as instruments, the study suggested increased levels of MAPKAPK3 (OR: 1.09; 95% CI: 1.05-1.13; P = 1.43 × 10^-6) and MRPL33 (OR: 1.07; 95% CI: 1.04-1.11; P = 5.37 × 10^-6) were causally associated with a higher risk of ASD, and increased MANBA level was associated with a lower risk of ADHD (OR: 0.91; 95% CI: 0.88-0.95; P = 8.97 × 10^-6). The causal associations were robust in sensitivity analysis, leave-one-out analysis and Multivariable MR, and no pleiotropy was observed. No significant risk protein was identified for TS.

Interpretation

The study findings support the idea that the MAPK/ERK signaling pathway and mitochondrial dysfunction are involved in the pathogenesis of ASD, while a deficiency in beta-mannosidase might play a role in the development of ADHD.

Funding

Natural Science Basic Research Program of Shaanxi (2021JQ-390).

SUBMITTER: Yang J

PROVIDER: S-EPMC8933670 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization analysis.

Yang Jian J He Xiaoyan X Qian Li L Zhao Binbin B Fan Yajuan Y Gao Fengjie F Yan Bin B Zhu Feng F Ma Xiancang X

EBioMedicine 20220317

<h4>Background</h4>Childhood neurodevelopmental disorders, including autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and Tourette syndrome (TS), comprise a major cause of health-related disabilities in children. However, biomarkers towards pathogenesis or novel drug targets are still limited. Our study aims to provide a comprehensive investigation of the causal effects of the plasma proteome on ASD, ADHD, and TS using the two-sample Mendelian Randomization (MR) a ...[more]

PMID: 35306338

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Dataset Information

Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization analysis.

Background

Methods

Findings

Interpretation

Funding

Publications

Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization analysis.

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