title: A multi-locus genetic association test for a dichotomous trait and its secondary phenotype.
abstract: Genetic association studies often collect information on secondary phenotypes related to the primary disease status. In many situations, the secondary phenotypes are only measured in subjects with the disease condition. It would be advantageous to model the primary trait and the secondary phenotype together if they share certain level of genetic heritability. We propose a family of multi-locus testing procedures to detect the composite association between a set of genetic markers and two traits (the primary trait and a secondary phenotype), in order to identify genes influencing both traits. The proposed test is derived from a random effect model with two variance components, with each presenting the genetic effect on one trait, and incorporates a model selection procedure for seeking the optimal model to represent the two sources of genetic effects. We conduct simulation studies to evaluate performance of the proposed procedure and apply the method to a genome-wide association study of prostate cancer with the Gleason score as the secondary phenotype.
authors: 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, USA.
authors: Han
authors: H
authors: Zhang
authors: 2 Office of Biostatistics Research, National Heart, Lung and Blood Institute, Bethesda, USA.
authors: Colin O
authors: CO
authors: Wu
authors: 3 Department of Statistics, University of Kentucky, Lexington, USA.
authors: Yifan
authors: Y
authors: Yang
authors: 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, USA.
authors: Sonja I
authors: SI
authors: Berndt
authors: 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, USA.
authors: Stephen J
authors: SJ
authors: Chanock
authors: 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, USA.
authors: Kai
authors: K
authors: Yu
mesh_terms: D056726:Genetic Association Studies / Q000379:methods*; D056426:Genetic Loci / Q000235:genetics; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D015233:Models, Statistical; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics; D019655:Quantitative Trait, Heritable
chemical_list: D005819:Genetic Markers
keywords: Secondary phenotype; genome-wide association study; multi-locus test; multiple testing; prostate cancer; variance component