Examination of association to autism of common genetic variationin genes related to dopamine

Autism is a severe neurodevelopmental disorder characterized by a triad of complications. Autistic individuals displaysignificant disturbances in language and reciprocal social interactions, combined with repetitive and stereotypicbehaviors. Prevalence studies suggest that autism is more common than originally believed, with recent estimates citing arate of one in 150. Although multiple genetic linkage and association studies have yielded multiple suggestive genes orchromosomal regions, a specific risk locus has yet to be identified and widely confirmed. Because many etiologies havebeen suggested for this complex syndrome, we hypothesize that one of the difficulties in identifying autism genes is thatmultiple genetic variants may be required to significantly increase the risk of developing autism. Thus, we took thealternative approach of examining 14 prominent dopamine pathway candidate genes for detailed study by genotyping 28single nucleotide polymorphisms. Although we did observe a nominally significant association for rs2239535 (P50.008)on chromosome 20, single-locus analysis did not reveal any results as significant after correction for multiplecomparisons. No significant interaction was identified when Multifactor Dimensionality Reduction was employed to testspecifically for multilocus effects. Although genome-wide linkage scans in autism have provided support for linkage tovarious loci along the dopamine pathway, our study does not provide strong evidence of linkage or association to anyspecific gene or combination of genes within the pathway. These results demonstrate that common genetic variationwithin the tested genes located within this pathway at most play a minor to moderate role in overall autism pathogenesis.