Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands

Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands

Abstract Autism spectrum disorder (ASD) presents a wide range of cognitive and language impairments. In this study, we investigated the genetic basis of non-verbal status in ASD using a comprehensive genomic approach. We identified a novel common variant, rs1944180 in CNTN5, significantly associated...

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Main Authors: Huan Liu, Shenghan Wang, Binbin Cao, Jijun Zhu, Zhifang Huang, Pan Li, Shunjie Zhang, Xian Liu, Jing Yu, Zhongting Huang, Linzhuo Lv, Fuqiang Cai, Weixin Liu, Zhijian Song, Yuxin Liu, Tao Pang, Suhua Chang, Ying Chen, Junfang Chen, Wen-Xiong Chen
Format: Article
Language:English
Published: BMC 2025-06-01
Series:Behavioral and Brain Functions
Subjects:
Autism spectrum disorder
Common variants
De Novo mutations
Whole-exome sequencing
Non-verbal status
Online Access:https://doi.org/10.1186/s12993-025-00278-x
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Summary:Abstract Autism spectrum disorder (ASD) presents a wide range of cognitive and language impairments. In this study, we investigated the genetic basis of non-verbal status in ASD using a comprehensive genomic approach. We identified a novel common variant, rs1944180 in CNTN5, significantly associated with non-verbal status through family-based Transmission Disequilibrium Testing. Polygenic risk score (PRS) analysis further showed that higher ASD PRS was significantly linked to non-verbal status (p = 0.034), specific to ASD and not related to other conditions such as bipolar disorder, schizophrenia and three language-related traits. Using structural equation modeling (SEM), we found two causal SNPs, rs1247761 located in KCNMA1 and rs2524290 in RAB3IL1, linking ASD with language traits. The model indicated a unidirectional effect, with ASD driving language impairments. Additionally, de novo mutations (DNMs) were found to be related with ASD and interaction between common variants and DNMs significantly impacted non-verbal status (p = 0.038). Our findings also identified 5 high-risk ASD genes, and DNMs were enriched in glycosylation-related pathways. These results offer new insights into the genetic mechanisms underlying language deficits in ASD.
ISSN:1744-9081

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