title: On rare-variant analysis in population-based designs: decomposing the likelihood to two informative components.
abstract: Various analytical approaches have been suggested for the characterization of rare variants. One main approach is to collapse the genetic information of rare variants in a region and to construct an overall test statistic. Here, we proposed a new approach based on collapsed genotype scores. By utilizing the information of the association signal that is ignored in collapsing methods, i.e. the configuration of rare alleles, we constructed a more powerful test and compared it with existing rare-variant approaches. With extensive simulation studies, we showed that our method performs better than existing approaches, and we applied our method to a sequencing study of nonsyndromic cleft lip illustrating the practical advantages of the proposed method.
authors.affiliation: Department of Applied Statistics, Chung-Ang University, Seoul, Korea.
authors.forename: Sungho
authors.initials: S
authors.lastname: Won
authors.forename: Youngdoe
authors.initials: Y
authors.lastname: Kim
authors.forename: Christoph
authors.initials: C
authors.lastname: Lange
mesh_terms: D002971:Cleft Lip / Q000235:genetics; D003198:Computer Simulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D008957:Models, Genetic; D035583:Rare Diseases / Q000235:genetics*