Genome-wide conditional search for epistatic disease-predisposing variants in human association studies.
Genome-wide search for new disease variants, based on well-established variants, has a long history in linkage analysis but is less well-known in genetic case-control association studies. We developed a simple yet highly efficient conditional search method that can find new variants, which are associated with a disease only through epistatic interaction with another variant and do not necessarily have a direct association effect. Our approach is analogous to partitioning of chi(2) in a hierarchical design, which is a well-established statistical technique. Applied to previously published data on age-related macular degeneration, our method found two single-nucleotide polymorphisms with genome-wide significant epistatic interaction that could not be found based only on direct main effects.
Wang
Gao
G
Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China.
Yang
Yaning
Y
Ott
Jurg
J
D004843:Epistasis, Genetic; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008962:Models, Theoretical; D020641:Polymorphism, Single Nucleotide