In a letter to Nature, Lauren Weiss, Dan Arking, the Gene Discovery Project of Johns Hopkins, and the Autism Consortium report that they have analyzed multiple data sets and identified potential loci on human genes for susceptibility for Autism. They found possible linkages on four chromosomes (5p15, 6q27, and 20p13) and, coupled with other data, the single nucleotide polymorphism on 5p15 pointed to SEMA5A as an important location for additional study. These results may lead to a means of screening; if rare variations can be identified reliably, they would permit families to seek intervention very early in the lives of affected individuals, thus greatly increasing the chances of improved outcomes.
Although autism is a highly heritable neurodevelopmental disorder, attempts to identify specific susceptibility genes have thus far met with limited success1. Genome-wide association studies using half a million or more markers, particularly those with very large sample sizes achieved through meta-analysis, have shown great success in mapping genes for other complex genetic traits. Consequently, we initiated a linkage and association mapping study using half a million genome-wide single nucleotide polymorphisms (SNPs) in a common set of 1,031 multiplex autism families (1,553 affected offspring). We identified regions of suggestive and significant linkage on chromosomes 6q27 and 20p13, respectively. Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 10-7). We also demonstrated that expression of SEMA5A is reduced in brains from autistic patients, further implicating SEMA5A as an autism susceptibility gene. The linkage regions reported here provide targets for rare variation screening whereas the discovery of a single novel association demonstrates the action of common variants.