01537nas a2200169   4500000000100000008004100001653001000042653001300052653001200065100001200077700001100089700001400100700001300114245012900127520109700256022001401353       2014                            d10aTests10agenotype10aleprosy1 aCobat A1 aAbel L1 aAlcaïs A1 aSchurr E00aA General Efficient and Flexible Approach for Genome-Wide Association Analyses of Imputed Genotypes in Family-Based Designs.3 a<p>Genotype imputation is a critical technique for following up genome-wide association studies. Efficient methods are available for dealing with the probabilistic nature of imputed single nucleotide polymorphisms (SNPs) in population-based designs, but not for family-based studies. We have developed a new analytical approach (FBATdosage), using imputed allele dosage in the general framework of family-based association tests to bridge this gap. Simulation studies showed that FBATdosage yielded highly consistent type I error rates, whatever the level of genotype uncertainty, and a much higher power than the best-guess genotype approach. FBATdosage allows fast linkage and association testing of several million of imputed variants with binary or quantitative phenotypes in nuclear families of arbitrary size with arbitrary missing data for the parents. The application of this approach to a family-based association study of leprosy susceptibility successfully refined the association signal at two candidate loci, C1orf141-IL23R on chromosome 1 and RAB32-C6orf103 on chromosome 6.</p>  a1098-2272