Investigation of WNT2, DISC1, and DOCK4 polymorphisms in a Turkish autism spectrum disorder cohort: a case-control...

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by social communication deficits and repetitive behaviors. The Wnt signaling pathway is a fundamental regulator of neural development, governing critical processes such as synapse formation and axonal guidance. Despite strong biological rationale, population-specific genetic data for Wnt-related candidate genes remain limited. This study investigated the association of WNT2 (rs4727847), DISC1 (rs4366301), and DOCK4 (rs2217262) polymorphisms with ASD in a Turkish population.

A case-control study was conducted involving 100 children diagnosed with ASD according to DSM-5 criteria and 100 healthy controls. Genotyping was performed using Real-Time PCR with TaqMan® assays. The groups were comparable in age (p = 0.774) and sex distribution (p = 0.883). Functional relevance was evaluated using bioinformatics analyses, including protein-protein interaction and pathway enrichment analyses. No statistically significant differences were observed in genotype frequencies between ASD and control groups for WNT2 (p = 0.850), DISC1 (p = 0.457), or DOCK4 (p = 0.542). None of the observed associations remained statistically significant after false discovery rate correction. Bioinformatics analyses indicated that all investigated variants were non-coding and functionally connected within SFARI-curated autism-associated molecular networks. GO and KEGG analyses demonstrated enrichment of neurodevelopment-related pathways after false discovery rate correction (adjusted p < 0.05).

Although no statistically significant genetic associations were identified in the present cohort, the bioinformatics findings suggest that these loci remain biologically relevant within Wnt-related pathways. Future functional and transcriptomic studies are needed to clarify their contribution to ASD susceptibility.