Given the advantages and difficulties of family- and case-control-based studies, we employed both the affected sibling pair (ASP) study approach (one type of family-based studies) and the case-control study approach, which we believe to be complementary, in the present study. Additionally, as allele frequency of variants often differs markedly in populations with different ancestral origins and a disease allele in one population may not exert any effect on the disease in another population, we examined the association of POMC variants with alcohol or drug dependence in both African Americans (AAs) and European Americans (EAs). In other words, four independent sets of samples (both AA and EA family samples and both AA and EA case-control samples) were included in this study.