Analysis of common genetic variants associated with neuro-synapse development among 60 family trios affected with sporadic autism spectrum disorders
10.3760/cma.j.issn.1003-9406.2020.01.001
- VernacularTitle: 散发孤独症谱系障碍核心家系神经-突触发育相关共有变异基因分析
- Author:
Jian JIAO
1
;
Manxue ZHANG
;
Pingyuan YANG
;
Yan HUANG
;
Xiao HU
;
Jia CAI
;
Chan YANG
;
Mingjing SI-TU
;
Hui ZHANG
;
Lei FU
;
Kuifang GUO
;
Yi HUANG
Author Information
1. Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China
- Publication Type:Journal Article
- Keywords:
Autism spectrum disorders;
Whole-exome sequencing;
Gene-phenotype association;
Pathway enrichment analysis
- From:
Chinese Journal of Medical Genetics
2020;37(1):1-4
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore susceptibility genes for autism spectrum disorders (ASD).
Methods:Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates.
Results:A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2 (0.8146)] and four medium-confidence genes [ERBB2 (0.1322), LAMC3 (0.1117), PPFIA4 (0.1059), DISC1 (0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes.
Conclusion:Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.
