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

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.

Reverse Pathway Genetic Approach Identifies Epistasis in Autism Spectrum Disorders

“…The encoded protein (FOX1) controls alternative splicing and transcription[114], including many other ASD candidate genes, and is thought to be a key regulator of neurodevelopment[115]. DISC1 , known for identification via rare structural variant in schizophrenia, has also been associated with ASDs[78,112,116,117]. Additional genes listed in SFARIgene[89] adjacent to our top RASopathy social responsiveness QTL results include CNTN5 , ESRRB , GABRB1 , GNB1L , and ICA1 .…”

The link between long noncoding RNAs and depression

“…The disruption of the Disrupted-in-Schizophrenia (DISC) genomic locus, has linked to the risk of developing schizophrenia (Hattori et al, 2014;Talib et al, 2014), schizoaffective disorder (Hodgkinson et al, 2004), major depression (Arias et al, 2014), and autistic spectrum disorders (Zheng et al, 2011). A t(1;11) translocation revealed genomewide significant linkage for schizophrenia, rMDD and together with BD (Thomson et al, 2014).…”

Disorders and borders: Psychiatric genetics and nosology

“…Analysis of the chromosome 1 breakpoint revealed disruption of a gene that was dubbed DISC1 (for Disrupted‐in‐Schizophrenia 1) [Millar et al, ]. Subsequent reports have also linked DISC1 to schizoaffective disorder and autism spectrum disorders [Hodgkinson et al, ; Hamshere et al, ; Kilpinen et al, ; Williams et al, ; Green et al, ; Zheng et al, ]. The biology of DISC1 has been studied in great detail and has revealed a complex network of interactions with other key molecules involved in neurodevelopment (including neuronal proliferatin and migration as well as synapse formation and stabilization), mitochondrial function, and cellular signaling [Brandon and Sawa, ].…”