Association between plasma proteome and childhood neurodevelopmental disorders: A two-sample Mendelian randomization analysis
Jian Yang, Xiaoyan He, Qian Li, Binbin Zhao, Yajuan Fan, Fengjie Gao, Bin Yan, Feng Zhu, Xiancang Ma
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: ). 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).