A traditional approach to family-based analysis of parents and a single affected offspring (trios) is to treat the transmitted alleles as the case genotype and the remaining possible but unrealized genotypes as pseudo-controls using CLR [21-24]; X-linked loci are treated analogously for alleles. As noted by Self et al. [23], conceptually the family-based design is essentially equivalent to a case–control study in which the controls are sampled from hypothetical siblings. Thus for the purpose of analysis both case–control and family-based designs can lead to strata, each consisting of a case and one or more controls.
