孟德尔随机化
自闭症谱系障碍
神经发育障碍
全基因组关联研究
医学
注意缺陷多动障碍
单核苷酸多态性
生物信息学
遗传学
肿瘤科
自闭症
精神科
基因型
生物
遗传变异
基因
作者
Jian Yang,Xijing He,Qian Li,Binbin Zhao,Yijun Fan,Fengjie Gao,Bin Yan,Feng Zhu,Xiancang Ma
出处
期刊:EBioMedicine
[Elsevier]
日期:2022-04-01
卷期号:78: 103948-103948
被引量:11
标识
DOI:10.1016/j.ebiom.2022.103948
摘要
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.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.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.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.Natural Science Basic Research Program of Shaanxi (2021JQ-390).
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