male cases and younger controls. To address this issue, we re-analyzed the data using backward stepwise logistic regression in which confounding factors (age and sex) were considered. The results obtained supported the findings from marker or haplotype association analyses. Third, case-control studies are vulnerable for Type I errors due to population stratification. To address this issue, we applied complementary family- and case-control-based approaches. Additionally, a panel of 38 AIMs were available for all family members (27) and a majority (96.1%) of the unrelated subjects (Figure 2), making it possible to classify these individuals as either genetic ‘AAs’ or genetic ‘EAs’. Thus, the positive results from our case-control studies were unlikely to have been driven by population stratification. However, this set of 38 AIMs may not have sufficient power to detect subtle allele frequency differences occurring within the same population group (e.g., allele frequency differences between Northern and Southern Europeans, or East and West Africans). Of particular note is the consistency of the findings from both family- and population-based approaches, which provide convergent validation of the association findings. Finally, the issue of cumulative multiple testing needs to be considered, because many of our samples (our family samples and SCID-III-R or SCID-IV
