Family-based association testing of glutamate transporter genes in autism

Glutamate transporters are critical for signaling and excitotoxicity because they regulate extracellular glutamate in the synapse. Four glutamate transporter genes, SLC1A1, SLC1A2, SLC1A3, and SLC1A6, are positional and functional candidates for autism. Studies have implicated SLC1A1 in obsessive-compulsive disorder (Arnold et al., 2006) and autism spectrum disorder (ASD) (Brune et al., 2008). Upregulation of SLC1A2 and SLC1A3 has been reported in brains of individuals with autism (Purcell et al., 2001). SLC1A2 is under the highest linkage peak in the Autism Genome Project scan (Szatmari et al., 2007). Both SLC1A3 and SLC1A6 are most abundantly expressed in cerebellum (Bridges and Esslinger, 2005) where structural and functional deficits occur in autism. On the basis of these lines of evidence, we hypothesized that variations in these four glutamate transporter genes confer risk for autism susceptibility.