title: SNP set association analysis for familial data.
abstract: Genome-wide association studies (GWAS) are a popular approach for identifying common genetic variants and epistatic effects associated with a disease phenotype. The traditional statistical analysis of such GWAS attempts to assess the association between each individual single-nucleotide polymorphism (SNP) and the observed phenotype. Recently, kernel machine-based tests for association between a SNP set (e.g., SNPs in a gene) and the disease phenotype have been proposed as a useful alternative to the traditional individual-SNP approach, and allow for flexible modeling of the potentially complicated joint SNP effects in a SNP set while adjusting for covariates. We extend the kernel machine framework to accommodate related subjects from multiple independent families, and provide a score-based variance component test for assessing the association of a given SNP set with a continuous phenotype, while adjusting for additional covariates and accounting for within-family correlation. We illustrate the proposed method using simulation studies and an application to genetic data from the Genetic Epidemiology Network of Arteriopathy (GENOA) study.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Schifano
authors.forename: Michael P
authors.initials: MP
authors.lastname: Epstein
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Bielak
authors.forename: Min A
authors.initials: MA
authors.lastname: Jhun
authors.forename: Sharon L R
authors.initials: SL
authors.lastname: Kardia
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Peyser
authors.forename: Xihong
authors.initials: X
authors.lastname: Lin
mesh_terms: D055573:Acid Ceramidase / Q000235:genetics; D000465:Algorithms; D001185:Artificial Intelligence; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D005190:Family; D005796:Genes / Q000235:genetics; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006801:Humans; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C526693:ASAH1 protein, human; D055573:Acid Ceramidase