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Genetic variant rs17225178 in the ARNT2 gene is associated with Asperger Syndrome.
Molecular Autism ( IF 6.2 ) Pub Date : 2015-02-27 , DOI: 10.1186/s13229-015-0009-0 Agnese Di Napoli 1 , Varun Warrier 1 , Simon Baron-Cohen 2 , Bhismadev Chakrabarti 3
Molecular Autism ( IF 6.2 ) Pub Date : 2015-02-27 , DOI: 10.1186/s13229-015-0009-0 Agnese Di Napoli 1 , Varun Warrier 1 , Simon Baron-Cohen 2 , Bhismadev Chakrabarti 3
Affiliation
BACKGROUND
Autism Spectrum Conditions (ASC) are neurodevelopmental conditions characterized by difficulties in communication and social interaction, alongside unusually repetitive behaviours and narrow interests. Asperger Syndrome (AS) is one subgroup of ASC and differs from classic autism in that in AS there is no language or general cognitive delay. Genetic, epigenetic and environmental factors are implicated in ASC and genes involved in neural connectivity and neurodevelopment are good candidates for studying the susceptibility to ASC. The aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) gene encodes a transcription factor involved in neurodevelopmental processes, neuronal connectivity and cellular responses to hypoxia. A mutation in this gene has been identified in individuals with ASC and single nucleotide polymorphisms (SNPs) have been nominally associated with AS and autistic traits in previous studies.
METHODS
In this study, we tested 34 SNPs in ARNT2 for association with AS in 118 cases and 412 controls of Caucasian origin. P values were adjusted for multiple comparisons, and linkage disequilibrium (LD) among the SNPs analysed was calculated in our sample. Finally, SNP annotation allowed functional and structural analyses of the genetic variants in ARNT2. We tested the replicability of our result using the genome-wide association studies (GWAS) database of the Psychiatric Genomics Consortium (PGC).
RESULTS
We report statistically significant association of rs17225178 with AS. This SNP modifies transcription factor binding sites and regions that regulate the chromatin state in neural cell lines. It is also included in a LD block in our sample, alongside other genetic variants that alter chromatin regulatory regions in neural cells.
CONCLUSIONS
These findings demonstrate that rs17225178 in the ARNT2 gene is associated with AS and support previous studies that pointed out an involvement of this gene in the predisposition to ASC.
中文翻译:
ARNT2 基因中的遗传变异 rs17225178 与阿斯伯格综合症有关。
背景自闭症谱系病症(ASC)是神经发育病症,其特征在于沟通和社交互动困难,以及异常重复的行为和狭隘的兴趣。阿斯伯格综合症 (AS) 是 ASC 的一个亚组,与经典自闭症的不同之处在于 AS 中没有语言或一般认知延迟。遗传、表观遗传和环境因素与 ASC 相关,参与神经连接和神经发育的基因是研究 ASC 易感性的良好候选者。芳烃受体核转位子 2 (ARNT2) 基因编码参与神经发育过程、神经元连接和细胞对缺氧反应的转录因子。已经在患有 ASC 的个体中发现了该基因的突变,并且在先前的研究中,单核苷酸多态性 (SNP) 名义上与 AS 和自闭症特征相关。方法 在这项研究中,我们在 118 例病例和 412 例白种人对照中测试了 ARNT2 中的 34 个 SNP 与 AS 的关联。针对多重比较调整 P 值,并在我们的样本中计算分析的 SNP 之间的连锁不平衡 (LD)。最后,SNP 注释允许对 ARNT2 中的遗传变异进行功能和结构分析。我们使用 Psychiatric Genomics Consortium (PGC) 的全基因组关联研究 (GWAS) 数据库测试了我们的结果的可复制性。结果 我们报告了 rs17225178 与 AS 的统计学显着关联。该 SNP 修饰调节神经细胞系中染色质状态的转录因子结合位点和区域。它也包含在我们样本的 LD 块中,以及其他改变神经细胞染色质调节区的遗传变异体。结论 这些发现表明 ARNT2 基因中的 rs17225178 与 AS 相关,并支持先前的研究指出该基因与 ASC 的易感性有关。
更新日期:2019-11-01
中文翻译:
ARNT2 基因中的遗传变异 rs17225178 与阿斯伯格综合症有关。
背景自闭症谱系病症(ASC)是神经发育病症,其特征在于沟通和社交互动困难,以及异常重复的行为和狭隘的兴趣。阿斯伯格综合症 (AS) 是 ASC 的一个亚组,与经典自闭症的不同之处在于 AS 中没有语言或一般认知延迟。遗传、表观遗传和环境因素与 ASC 相关,参与神经连接和神经发育的基因是研究 ASC 易感性的良好候选者。芳烃受体核转位子 2 (ARNT2) 基因编码参与神经发育过程、神经元连接和细胞对缺氧反应的转录因子。已经在患有 ASC 的个体中发现了该基因的突变,并且在先前的研究中,单核苷酸多态性 (SNP) 名义上与 AS 和自闭症特征相关。方法 在这项研究中,我们在 118 例病例和 412 例白种人对照中测试了 ARNT2 中的 34 个 SNP 与 AS 的关联。针对多重比较调整 P 值,并在我们的样本中计算分析的 SNP 之间的连锁不平衡 (LD)。最后,SNP 注释允许对 ARNT2 中的遗传变异进行功能和结构分析。我们使用 Psychiatric Genomics Consortium (PGC) 的全基因组关联研究 (GWAS) 数据库测试了我们的结果的可复制性。结果 我们报告了 rs17225178 与 AS 的统计学显着关联。该 SNP 修饰调节神经细胞系中染色质状态的转录因子结合位点和区域。它也包含在我们样本的 LD 块中,以及其他改变神经细胞染色质调节区的遗传变异体。结论 这些发现表明 ARNT2 基因中的 rs17225178 与 AS 相关,并支持先前的研究指出该基因与 ASC 的易感性有关。