Genetic Risk of Autism Spectrum Disorder in a Pakistani Population

Abstract

Autism spectrum disorder (ASD) is a group of complex multifactorial neurodevelopmental and neuropsychiatric disorders in children characterized by impairment of communication and social interaction. Several genes with associated single nucleotide polymorphisms (SNPs) have been identified for ASD in different genetic association studies, meta-analyses, and genome-wide association studies (GWAS). However, associations between different SNPs and ASD vary from population to population. Four SNPs in genes CNTNAP2, EIF4E, ATP2B2, CACNA1C, and SNP rs4307059 (which is found between CDH9 and CDH10 genes) have been identified and reported as candidate risk factors for ASD. The aim of the present study was, for the first time, to assess the association of SNPs in these genes with ASD in the Pakistani population. PCR-based genotyping was performed using allele-specific primers in 93 ASD and 93 control Pakistani individuals. All genetic associations, genotype frequencies, and allele frequencies were computed as odds’ ratios (ORs) using logistic regression with a threshold of p ≤ 0.01 to determine statistical significance. We found that the homozygous genotypes of mutant T alleles of CNTNAP2 and ATP2B2 were significantly associated with Pakistani ASD patients in unadjusted ORs (p < 0.01), but their significance score was lost in the adjusted model. Other SNPs such as rs4307059, rs17850950 of EIF4E, and rs1006737 of CACNA1C were not statistically significant. Based on this, we conclude that SNPs are not associated with, or are not the main cause of, autism in the Pakistani population, indicating the involvement of additional players, which need to be investigated in future studies in a large population size. One of the limitations of present study is its small sample size. However, this study, being the first on Pakistani ASD patients, may lay the foundations for future studies in larger samples.

A case-control study along with an epidemiological approach to CNTNAP2 polymorphism among Bangladeshi ASD children

“…Researchers found that despite the absence of behavioral abnormalities homozygotes for the risk allele (T) showed significant cerebral morphological variation, including reductions in grey and white matter volume in several regions (cerebellum, fusiform gyrus, and occipital and frontal cortices) that have already been implicated in ASD, suggesting that this polymorphism could disrupt frontal-occipital connections (Peñagarikano and Geschwind, 2012). In the Pakistani population, it was shown that A/T in rs7794745 of CNTNAP2 is a risk genotype for ASD (Khalid et al, 2020). According to (Nascimento et al, 2016), a research finding on the Brazilian population reported this SNP is a susceptible factor for the Brazilian population while (Werling et al, 2016) found no association with the population of Zurich.…”

Comparison of Visual Functions and Ocular Health in Children with Autism Spectrum Disorder versus Typically Developing Peers

“…1 It is mainly caused by chromosomal abnormalities, gene mutations and exposure of offspring to viral or bacterial infection. 2 In recent years, ASD has shown an increase in prevalence. The American Academy of Pediatrics has reported a prevalence rate of 1 outof 91 children in the age group of 3-17 years.…”

Walking with the spectrum: A phenomenological study on the experiences of mothers raising an Autistic child

“…This paper aims to explore the mothers' experiences, their conceptions about autism and how they interact with the child in relation to the world around them. Examining mothers' experiences raising an Autistic child in Pakistan has been challenging; as parents are often surrounded by the social stigma surrounding mental disorders (Khalid et al, 2020). This results in under reporting such cases, which makes new parents of an Autistic child feel further alienated.…”