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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| Format: | Article |
| Language: | English |
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BMC
2025-06-01
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| Series: | Behavioral and Brain Functions |
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| Online Access: | https://doi.org/10.1186/s12993-025-00278-x |
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| author | 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 |
| author_facet | 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 |
| author_sort | Huan Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8f0cdd32fe9a4bb093dc4729014efcdf |
| institution | OA Journals |
| issn | 1744-9081 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Behavioral and Brain Functions |
| spelling | doaj-art-8f0cdd32fe9a4bb093dc4729014efcdf2025-08-20T02:05:14ZengBMCBehavioral and Brain Functions1744-90812025-06-0121111110.1186/s12993-025-00278-xUnraveling genetic risk contributions to nonverbal status in autism spectrum disorder probandsHuan Liu0Shenghan Wang1Binbin Cao2Jijun Zhu3Zhifang Huang4Pan Li5Shunjie Zhang6Xian Liu7Jing Yu8Zhongting Huang9Linzhuo Lv10Fuqiang Cai11Weixin Liu12Zhijian Song13Yuxin Liu14Tao Pang15Suhua Chang16Ying Chen17Junfang Chen18Wen-Xiong Chen19Department of Behavioral Development, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityCenter for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan UniversityDepartment of Neurology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityCenter for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan UniversityDepartment of Behavioral Development, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityCenter for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan UniversityCenter for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan UniversityDepartment of Behavioral Development, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Behavioral Development, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityCenter for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan UniversityDepartment of Behavioral Development, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversitySchool of Biology and Biological Engineering, South China University of TechnologySchool of Biology and Biological Engineering, South China University of TechnologySchool of Biology and Biological Engineering, South China University of TechnologyCenter for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan UniversityNHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)NHC Key Laboratory of Mental Health (Peking University), Peking University Sixth Hospital, Peking University Institute of Mental Health, National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital)Department of Behavioral Development, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityCenter for Intelligent Medicine, Greater Bay Area Institute of Precision Medicine (Guangzhou), School of Life Sciences, Fudan UniversityDepartment of Behavioral Development, Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityAbstract 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.https://doi.org/10.1186/s12993-025-00278-xAutism spectrum disorderCommon variantsDe Novo mutationsWhole-exome sequencingNon-verbal status |
| spellingShingle | 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 Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands Behavioral and Brain Functions Autism spectrum disorder Common variants De Novo mutations Whole-exome sequencing Non-verbal status |
| title | Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands |
| title_full | Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands |
| title_fullStr | Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands |
| title_full_unstemmed | Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands |
| title_short | Unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands |
| title_sort | unraveling genetic risk contributions to nonverbal status in autism spectrum disorder probands |
| topic | Autism spectrum disorder Common variants De Novo mutations Whole-exome sequencing Non-verbal status |
| url | https://doi.org/10.1186/s12993-025-00278-x |
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