To determine if we might miss a strong signal by only using the CAP dataset as the discovery dataset, we also reversed the datasets for discovery and validation and used our same two stage approach. 21 SNPs had p-values < 0.0001 in the AGRE dataset but none of them could be replicated in CAP dataset even with a nominal significance of p<0.05. We computed the power of the TDT in 438 triad families that approximates a lower bound for power of the PDT in our discovery sample. Given a prevalence of autism of 0.0066 (Chakrabarti, Fombonne 2005), a SNP in LD (D'=1) with a risk allele frequency 0.6, we expect 84% power to detect an association at p =0.0001 under a recessive model (GRRAA=2, GRRAa=1) and 33% under additive model (GRRAA=2, GRRAa=1.5). These are consistent with the allelic GRR's estimated for the chromosome 5 region. The power to detect a Bonferroni-corrected genome-wide significance (p = 0.05 / 775311 SNPs = 6.4×10-8) drops to 30% and 2.5%, respectively, for recessive and additive models.
