While we and others (20,21) find limited evidence that common alleles affect risk for autism, the number of families studied is still relatively small. Our findings appear to rule out a common allele increasing relative risk by 2-fold or more. Much larger samples will be required to detect subtle effects on relative risk (e.g. 1.2), which is more typical of risk loci for common diseases. With such low relative risk, replication of true positive findings is further complicated by chance findings, as well as differences in ascertainment. These challenges are not unique to common variants. The same challenges are faced when searching for rare sequence mutations and CNVs affecting risk for ASD. Moreover, our ultimate goal is to integrate results across the range of rare to common variation, thereby describing the genetic architecture of autism. This will require larger cohorts comprised of individuals exhibiting the relatively stringent ASD phenotype of this study, as well as an unselected group more representative of the general ASD population, both being examined at the highest resolution for CNVs, rare sequence variation and common alleles.
