title: Testing for direct genetic effects using a screening step in family-based association studies.
abstract: In genome wide association studies (GWAS), family-based studies tend to have less power to detect genetic associations than population-based studies, such as case-control studies. This can be an issue when testing if genes in a family-based GWAS have a direct effect on the phenotype of interest over and above their possible indirect effect through a secondary phenotype. When multiple SNPs are tested for a direct effect in the family-based study, a screening step can be used to minimize the burden of multiple comparisons in the causal analysis. We propose a 2-stage screening step that can be incorporated into the family-based association test (FBAT) approach similar to the conditional mean model approach in the Van Steen-algorithm (Van Steen et al., 2005). Simulations demonstrate that the type 1 error is preserved and this method is advantageous when multiple markers are tested. This method is illustrated by an application to the Framingham Heart Study.
authors: Department of Biostatistics, University of Colorado Aurora, CO, USA ; Department of Biostatistics, Harvard School of Public Health Boston, MA, USA.
authors: Sharon M
authors: SM
authors: Lutz
authors: Stijn
authors: S
authors: Vansteelandt
authors: Christoph
authors: C
authors: Lange
keywords: causal inference; family-based association analysis; genetic pathway; mediation; pleiotropy