Genetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population
Abstract Multiple epidermal growth factor-like-domains 10 (MEGF10), a critical member of the apoptotic engulfment pathway, mediates axon pruning and synapse elimination during brain development. Previous studies indicated that synaptic pruning deficit was associated with autism-related phenotypes. H...
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Nature Portfolio
2017
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oai:doaj.org-article:165798ae1fd54a70a205526485ea507d2021-12-02T12:32:08ZGenetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population10.1038/s41598-017-02348-12045-2322https://doaj.org/article/165798ae1fd54a70a205526485ea507d2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02348-1https://doaj.org/toc/2045-2322Abstract Multiple epidermal growth factor-like-domains 10 (MEGF10), a critical member of the apoptotic engulfment pathway, mediates axon pruning and synapse elimination during brain development. Previous studies indicated that synaptic pruning deficit was associated with autism-related phenotypes. However, the relationship between MEGF10 and autism remains poorly understood. Disease-associated variants are significantly enriched in the transcription regulatory regions. These include the transcription start site (TSS) and its cis-regulatory elements. To investigate the role of MEGF10 variants with putative transcription regulatory function in the etiology of autism, we performed a family-based association study in 410 Chinese Han trios. Our results indicate that three single nucleotide polymorphisms (SNPs), rs4836316, rs2194079 and rs4836317 near the TSS are significantly associated with autism following Bonferroni correction (p = 0.0011, p = 0.0088, and p = 0.0023, respectively). Haplotype T-A-G (rs4836316-rs2194079-rs4836317) was preferentially transmitted from parents to affected offspring (p permutation = 0.0055). Consistently, functional exploration further verified that the risk allele and haplotype might influence its binding with transcription factors, resulting in decreased transcriptional activity of MEGF10. Our findings indicated that the risk alleles and haplotype near the MEGF10 TSS might modulate transcriptional activity and increase the susceptibility to autism.Zhiliu WuJian QinYang YouYuanlin MaMeixiang JiaLinyan WangTianlan LuWeihua YueYanyan RuanDai ZhangJun LiLifang WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017) |
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Medicine R Science Q Zhiliu Wu Jian Qin Yang You Yuanlin Ma Meixiang Jia Linyan Wang Tianlan Lu Weihua Yue Yanyan Ruan Dai Zhang Jun Li Lifang Wang Genetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population |
| description |
Abstract Multiple epidermal growth factor-like-domains 10 (MEGF10), a critical member of the apoptotic engulfment pathway, mediates axon pruning and synapse elimination during brain development. Previous studies indicated that synaptic pruning deficit was associated with autism-related phenotypes. However, the relationship between MEGF10 and autism remains poorly understood. Disease-associated variants are significantly enriched in the transcription regulatory regions. These include the transcription start site (TSS) and its cis-regulatory elements. To investigate the role of MEGF10 variants with putative transcription regulatory function in the etiology of autism, we performed a family-based association study in 410 Chinese Han trios. Our results indicate that three single nucleotide polymorphisms (SNPs), rs4836316, rs2194079 and rs4836317 near the TSS are significantly associated with autism following Bonferroni correction (p = 0.0011, p = 0.0088, and p = 0.0023, respectively). Haplotype T-A-G (rs4836316-rs2194079-rs4836317) was preferentially transmitted from parents to affected offspring (p permutation = 0.0055). Consistently, functional exploration further verified that the risk allele and haplotype might influence its binding with transcription factors, resulting in decreased transcriptional activity of MEGF10. Our findings indicated that the risk alleles and haplotype near the MEGF10 TSS might modulate transcriptional activity and increase the susceptibility to autism. |
| format |
article |
| author |
Zhiliu Wu Jian Qin Yang You Yuanlin Ma Meixiang Jia Linyan Wang Tianlan Lu Weihua Yue Yanyan Ruan Dai Zhang Jun Li Lifang Wang |
| author_facet |
Zhiliu Wu Jian Qin Yang You Yuanlin Ma Meixiang Jia Linyan Wang Tianlan Lu Weihua Yue Yanyan Ruan Dai Zhang Jun Li Lifang Wang |
| author_sort |
Zhiliu Wu |
| title |
Genetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population |
| title_short |
Genetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population |
| title_full |
Genetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population |
| title_fullStr |
Genetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population |
| title_full_unstemmed |
Genetic variants in the transcription regulatory region of MEGF10 are associated with autism in Chinese Han population |
| title_sort |
genetic variants in the transcription regulatory region of megf10 are associated with autism in chinese han population |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/165798ae1fd54a70a205526485ea507d |
| work_keys_str_mv |
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