The initial TDT analysis of this large multiplex autism dataset, did not reveal any associations meeting criteria for genome-wide significance, suggesting that there are not many common loci of moderate to large effect size even in a highly heritable disorder like autism. Nevertheless, replication data in our study identified a novel locus with genome-wide significant evidence for association to autism. In addition, several other SNPs in the region show similarly strong association (rs10513026, rs16883317). We ascertained a large replication sample from independent family studies with a replication at P = 0.0061 and meta-analysis showed this association (P = 2.12 × 10−7) to meet criteria for genome-wide association in our experiment. This region on chromosome 5 harbors the gene encoding the bitter taste receptor, TAS2R1, and several uncharacterized ESTs and is adjacent to SEMA5A, a member of the semaphorin axonal guidance protein family, which has shown down-regulated expression in transformed B lymphocytes from autism samples15. We have further extended this finding by directly demonstrating lowered SEMA5A gene expression in autism brain tissue. This is an attractive candidate gene given that its
