Family-based approaches: design, imputation, analysis, and beyond

摘要

Participants in the family-based analysis group at Genetic Analysis Workshop 19 addressed diverse topics, all of which used the family data. Topics addressed included questions of study design and data quality control (QC), genotype imputation to augment available sequence data, and linkage and/or association analyses. Results show that pedigree-based tests that are sensitive to genotype error may be useful for QC. Imputation quality improved with inclusion of small amounts of pedigree information used to phase the data in evaluation of 5 commonly used approaches for imputation in samples of (typically) unrelated subjects. It improved still further when pedigree-based imputation using larger pedigrees was also added. An important distinction was made between methods that do versus do not make use of Mendelian transmission in pedigrees, because this serves as a key difference between underlying models and assumptions. Methods that model relatedness generally had higher power in association testing than did analyses that carry out testing in the presence of a transmission model, but this may reflect details of implementation and/or ability of more general methods to jointly include data from larger pedigrees. In either case, for single nucleotide polymorphism–set approaches, weights that incorporate information on functional effects may be more useful than those that are based only on allele frequencies. The overall results demonstrate that family data continue to provide important information in the search for trait loci.