| This dissertation concerns family-based genetic linkage analysis in the presence of missing parental genotypes. Parental marker genotypes might be unavailable, particularly for the study of diseases with late age of onset. To utilize family data with incomplete parental information, we propose a reconstruction-combined transmission disequilibrium/heterogeneity (RC-TDH) test, which extends the RC-TDT proposed by Knapp (1999) and the sib-TDT (and C-TDT) by Spielman and Ewens (1998). The proposed RC-TDH test does not require any knowledge of penetrance parameters, population allele frequencies, mating types, or the extent of linkage disequilibrium. Applications of the proposed methodology to a dataset from the Genetic Analysis Workshop 14 (GAW14) and our simulation studies show that the proposed RC-TDH may have increased statistical power over the RC-TDT to detect linkage, particularly when linkage disequilibrium is not strong. |
