Many complex diseases have recently had great success with GWAS approaches, but most identified modest effects with odds ratios less than 1.3 (http://www.genome.gov/26525384). Our association analysis has excellent statistical power (>80%) to find effects of relatively common alleles (0.01–0.25 in frequency) explaining 1% of the variance in autism at the genome-wide significant level. It is near-perfectly powered for alleles down to 1% at the replication cut-off P < 10−4, assuming additive background genetic variance of 0.8 and shared environmental variance of 0.05 with prevalence of 0.006. One of the advantages of a family-based association test is that we avoid false positive results generated by population stratification, and in addition, we have performed careful quality control to reduce the chances of being misled by technical artifacts. However, the SNP coverage of the Affymetrix 5.0 chips is incomplete; in fact, a recent resequencing survey suggests that these arrays assay only 57% of variants with MAF > 5% at r2 = 0.8 15. We therefore cannot exclude untested variation of large effect in autism. The linkage analysis, assuming a fully informative marker in 800 sibpairs, should detect sibling allele sharing of at least 55.125% 16.
