Abstract
BackgroundDisrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that DISC1 polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether DISC1 is associated with autism in Chinese Han population, we performed a family-based association study between DISC1 polymorphisms and autism.MethodsWe genotyped seven tag single nucleotide polymorphisms (SNPs) in DISC1, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software.ResultsWe found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, p = 0.004; rs11585959: T > C, Z = 2.199, p = 0.028; rs6668845: A > G, Z = 2.326, p = 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of DISC1, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical p values.ConclusionsOur study provided evidence that the DISC1 may be the susceptibility gene of autism. It suggested DISC1 might play a role in the pathogenesis of autism.
Highlights
Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders
We tested a total of seven single nucleotide polymorphisms (SNPs) over the 338 kb region of 1q42 with DISC1 in 367 Chinese Han autism trios
All seven SNPs were polymorphic with minor allele frequency (MAF) >5% and were used as genetic markers for the association study
Summary
Disrupted-in-Schizophrenia 1 (DISC1) gene is one of the most promising candidate genes for major mental disorders. Functional MRI studies in autism patients have indicated that alterations in task related connectivity, including enhanced activation and connectivity in posterior areas, enhanced reliance on visuospatial abilities for verbal and visual reasoning and reduced frontal systems connectivity [17,18,19,20,21]. All together, these previous studies suggested that abnormalities of neurodevelopment might be the etiology of autism. Considering the heritability of autism is relatively high, genes which play important roles in neurodevelopment might be candidate genes for autism
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