Our power calculation shows that stringent adjustments for multiple testing provide power only to detect loci with large effects given our sample size. Lowering the threshold for significance allows detection of loci with relatively small effects (such as the chromosome 5 locus), while also relying on replication to limit the false positives. We note that this region of 5p14.1 did not generate exceptional p-values in our initial GWAS, suggesting that a strong single gene association, such as those seen with APOE gene in Alzheimer disease { and CFH gene in age related macular degeneration (International Multiple Sclerosis Genetics Consortium et al. 2007) is highly unlikely in autism. The absence of a large effect is consistent with the results of previously published linkage studies (Ma et al. 2007, Allen-Brady et al. 2008). Only through the analysis of the validation dataset were we able to identify this replicated signal, highlighting the value of both a validation dataset and of joint analyses. Two additional datasets have found association of autism at 5p14.1. These include a cohort of 1,241 ASD cases and 6,491 control
