Genetic variant rs17225178 in the ARNT2 gene is associated with Asperger Syndrome

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• 作者：Agnese Di Napoli (1)
  Varun Warrier (1)
  Simon Baron-Cohen (1) (2)
  Bhismadev Chakrabarti (3)
  
  1. Department of Psychiatry ; Autism Research Centre ; University of Cambridge ; Douglas House ; 18B Trumpington Road ; Cambridge ; CB2 8AH ; UK
  2. Cambridgeshire and Peterborough NHS Foundation Trust ; CLASS Clinic ; Cambridge ; UK
  3. Centre for Integrative Neuroscience and Neurodynamics ; School of Psychology and Clinical Language Sciences ; University of Reading ; Reading ; UK
  
• 关键词：Autism spectrum conditions (ASC) ; Asperger Syndrome (AS) ; Aryl ; hydrocarbon receptor nuclear translocator 2 (ARNT2) ; Single nucleotide polymorphisms (SNPs)
• 刊名：Molecular Autism
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：6
• 期：1
• 全文大小：786 KB
• 参考文献：DSM-IV Diagnostic and Statistical Manual of Mental Disorders, Text revision. American Psychiatric Association, Washington, DC
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• 刊物主题：Neurology; Neurosciences; Neuropsychology; Molecular Medicine; Psychiatry; Pediatrics;
• 出版者：BioMed Central
• ISSN：2040-2392

文摘

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.