We next evaluated completeness and coverage for the hypothesis-driven candidate genes. First, we estimated statistical power to detect association. Even for relatively large studies (i.e., samples sizes at the 90th percentiles of Ncase=537 and Ncontrol=628) and a liberal correction for multiple comparisons (α=0.005, 10 markers), power was 48% to detect genetic effects typical for GWAS of human diseases (median genotypic relative risk=1.28 and median minor allele frequency of 0.29 for disease associations with p<5×10−8) (Hindorff et al., 2009). Second, we assessed genomic coverage. The 732 hypothesis-driven candidate genes represent 3.7% of RefSeq autosomal genes (Pruitt et al., 2005). Marker coverage can be assessed only generally, but included only small proportions of common genetic variation. Finally, of all genes comprising pathways in the top four DAVID annotation clusters, only 6.7% had ever been studied. Although these pathways may be over-inclusive, the main hypotheses guiding selection of hypothesis-driven candidate genes were evaluated incompletely.
