Evidence for association between Disrupted-in-schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study

We 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.We 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.Our 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.Autism is a severe neurodevelopmental disorder mainly characterized by impairment in social interaction, communicative deficits, and repetitive and stereotyped patterns of behaviors or interests [1]. Since autism was first described as a disorder by Dr. Leo Kanner in 1943 [2], the speculation about its etiology has become an intriguing field which attracts a large number of scientists. To date, compelling evidence from twin and family studies has indicated a strong genetic involvement in the etiology of autism and the estimated heritability is over 90% [3-7]. However, the genetic etiology remains elusive.Several lines of evidence from postmortem [8-10] and structural magnetic resonance imaging (MRI) [11-16] supported the existence of brain abnormality in autism. It indicated that brain abnormalities in autism are not limited to a single brain area but involve different structures within a globally affected neuronal network. Furthermore, functional MRI studies in autism patients have indicated tha