Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands
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.
Authors
- Junfang Chen
- Suhua Chang (ORCID: https://orcid.org/0000-0001-7465-3985)
- Wen‐Xiong Chen (ORCID: https://orcid.org/0000-0001-9076-2006)
- Jijun Zhu
- Binbin Cao (ORCID: https://orcid.org/0000-0001-9660-2062)
- Fuqiang Cai
- Zhifang Huang (ORCID: https://orcid.org/0009-0005-2619-1911)
- Shunjie Zhang (ORCID: https://orcid.org/0000-0002-5407-1424)
- Huan Liu (ORCID: https://orcid.org/0000-0003-2226-3699)
- Xian Liu (ORCID: https://orcid.org/0000-0002-1662-477X)
- Ying‐Yeh Chen (ORCID: https://orcid.org/0000-0001-5543-5704)
- Yuxin Liu (ORCID: https://orcid.org/0000-0001-8191-1145)
- Weixin Liu (ORCID: https://orcid.org/0000-0002-1650-0371)
- Jing Yu (ORCID: https://orcid.org/0009-0009-3028-9312)
- Shenghan Wang (ORCID: https://orcid.org/0000-0002-4472-3986)
- Tao Pang
- Li Pan (ORCID: https://orcid.org/0000-0001-8927-9535)
- Long Lv
- Zhijian Song
- Zhongting Huang
Institutions
- Peking University (CN)
- Fudan University (CN)
- Guangzhou Women and Children Medical Center (CN)
- Peking University Sixth Hospital (CN)
- South China University of Technology (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Behavioral and Brain Functions
- Published
- 2025-06-07
- DOI
- https://doi.org/10.1186/s12993-025-00278-x
- Citations
- 1
- Primary Topic
- Autism Spectrum Disorder Research
- Type
- article
- Field-Weighted Citation Impact
- 1.43
Funders
- Natural Science Foundation of Guangdong Province
- Guangzhou Municipal Science and Technology Project
- National Social Science Fund of China