Genome-wide genetic heterogeneity discovery with categorical covariates.

Felipe Llinares-López, Laetitia Papaxanthos, Dean A. Bodenham, Damian Roqueiro, COPDGene Investigators, Karsten M. Borgwardt

Abstract: Genetic heterogeneity is the phenomenon that distinct genetic variants may give rise to the same phenotype. The recently introduced algorithm Fast Automatic Interval Search (FAIS) enables the genome-wide search of candidate regions for genetic heterogeneity in the form of any contiguous sequence of variants, and achieves high computational efficiency and statistical power. Although FAIS can test all possible genomic regions for association with a phenotype, a key limitation is its inability to correct for confounders such as gender or population structure, which may lead to numerous false-positive associations.