Another aspect of genetic studies such as ours with several investigated phenotypes that requires discussion is the multiple comparison problem. In these studies, the multiple statistical tests are clearly not independent of one another given linkage disequilibrium between variants (Table 1) and the high correlation between subphenotypes (hoarding in this case) and the general diagnosis of OCD. Therefore, methods that correct by the total number of tests (eg, the Bonferroni procedure) would be more conservative than appropriate in our view. We conducted empirical family-wise error correction for the categorical single-marker and haplotype analyses by permutation and determined that 2 haplotypes remain significant (H4 and H2) (Table 2). The significance values for our subphenotype analyses are nominally robust (for association of rs3933331 with Y-BOCS score, P=.005, and with SIR-assessed hoarding, P=.009) (Figure 4). They would, however, not withstand Bonferroni correction and therefore need to be interpreted with caution and observed in larger samples in future studies.
