Abstract
The clinical heterogeneity of autism spectrum disorder (ASD) is closely associated with the diversity of genes related to ASD pathogenesis. With their low effect size, it has been hard to define the role of common variants of genes in ASD phenotype. In this study, we reviewed genetic results and clinical scores widely used for ASD diagnosis to investigate the role of genes in ASD phenotype considering their functions in molecular pathways. Genetic data from next-generation sequencing (NGS) were collected from 94 participants with ASD. We analyzed enrichment of cellular processes and gene ontology using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We compared clinical characteristics according to genetic functional characteristics. We found 266 genes containing nonsense, frame shift, missense, and splice site mutations. Results from DAVID revealed significant enrichment for “ion channel” with an enrichment score of 8.84. Moreover, ASD participants carrying mutations in ion channel-related genes showed higher total IQ (p = 0.013) and lower repetitive, restricted behavior (RRB)-related scores (p = 0.003) and mannerism subscale of social responsiveness scale scores, compared to other participants. Individuals with variants in ion channel genes showed lower RRB scores, suggesting that ion channel genes might be relatively less associated with RRB pathogenesis. These results contribute to understanding of the role of common variants in ASD and could be important in the development of precision medicine of ASD.
Highlights
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose essential features include persistent impairment in reciprocal social communication and restricted, repetitive behaviors and interests (American Psychiatric Association and DSM-5 Task Force., 2013)
30 genes were involved in the ion channel cluster: CACNG2, CACNA1A, CACNA1C, CACNA1D, CACNA1G, and CACNA1H were associated with calcium voltage-gated channels; SCN1A, SCN10A, SCN2A, SCN3A, SCN7A, SCN9A, and SCN1B were involved in sodium voltage-gated channels; KCNMA1, KCNT1, KCNH2, KCNQ2, KCNQ4, HCN1, HCN2, FIGURE 1 | Participants and gene selection
We examined the role of common genetic variants in ASD phenotype by comparing clinical scores in ASD children with different genetic characteristics
Summary
Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose essential features include persistent impairment in reciprocal social communication and restricted, repetitive behaviors and interests (American Psychiatric Association and DSM-5 Task Force., 2013). Ion Channel Genes in Autism treatments applied for ASD patients, pharmacotherapy has proven effective in reducing behavioral problems associated with ASD (DeFilippis and Wagner, 2016). Previous studies have reported that over 30% of ASD patients used at least one antipsychotic drug and that the use of medication tends to be higher in ASD children (Rosenberg et al, 2010; Schubart et al, 2014). Medications are more often prescribed if ASD patients are diagnosed of other comorbid psychiatric illnesses, and antipsychotics are the most frequently prescribed pharmacotherapy in ASD with intellectual disability (Houghton et al, 2017)
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