title: Genotype-Based Score Test for Association Testing in Families.
abstract: The multiplex-case and control design in which multiple cases are sampled from the same family is considered. In such studies phenotype information of the un-genotyped relatives might be available. We intend to use additional family information when performing genetic association tests. A score test is revisited to provide a flexible framework to accommodate various genetic models and to improve power of the association test by adding available family information. The proposed test accounts for correlations induced by multiple cases from the same pedigree, directly deals with X-linked SNPs in mixed-sex-related samples, and incorporates additional phenotypic information such as the number of (un-genotyped) siblings and parents with similar symptoms by assigning the weights to (genotyped) multiplex cases. In addition, the score test directly incorporates posterior probabilities of imputed genotypes, which leads to an efficiency measure that reflects imputation uncertainty on the test conducted. The proposed test is applied to real applications for illustration. Its efficiency is demonstrated via simulations.
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, S-5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Hae-Won
authors.initials: HW
authors.lastname: Uh
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, S-5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Marian
authors.initials: M
authors.lastname: Beekman
authors.affiliation: Department of Molecular Epidemiology, Leiden University Medical Center, S-5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meulenbelt
authors.affiliation: Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, S-5-P, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: Jeanine J
authors.initials: JJ
authors.lastname: Houwing-Duistermaat
keywords: Ascertained familial cases; Incorporation of additional family information; Multiplex-case and control design; Score test; X-linked SNPs; imputation uncertainty