A Single Nucleotide Polymorphism in the ARHGEF6 Gene is Associated with Increased Risk for Autism Spectrum Disorder

Background: Autism Spectrum Disorder (ASD) comprises a range of neurological conditions that can be a lifelong developmental disability. ASD is characterized by deficits in social communication and interaction with repetitive patterns of behavior and interests. Methods: The study population consisted of 155 ASD subjects (134 males, 21 females) selected randomly from Great Plains Laboratory subjects (84 males and 21 females) as well as from the Autism Genetic Resource Exchange (50 male subjects). Subjects were diagnosed by the CARS, DSM-IV, ABC, ADI-R, ADOS, PL-ADOS, or the BSE criteria for pervasive developmental ailment and Childhood Autism Rating Scale. A total of 247 individuals were used as controls (106 males, 141 females). Results: In our study we identified a single nucleotide polymorphism (SNP), rs2295868 in the ARHGEF6 gene (Rac/Cdc42 Guanine Nucleotide Exchange Factor 6) that was present in 36% of patients with ASD vs. 9% of controls. ARHGEF6, a Rho GTPase, is expressed mainly in the brain, immune system, and intestines. Conclusion: SNP rs2295868 on the ARHGEF6 gene has significant association with ASD (odds ratio 4.09, p=2.31 × 10-4).