Testing for direct genetic effects using a screening step in family-based association studies

• Main Authors: Sharon M Lutz, Stijn eVansteelandt, Christoph eLange
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2013-11-01
• Series: Frontiers in Genetics
• Subjects: causal inference; Family-based association analysis; Mediation; pleiotropy; genetic pathway
• Online Access: http://journal.frontiersin.org/Journal/10.3389/fgene.2013.00243/full

In genome wide association studies (GWAS), families 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 or if the genes act indirectly 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 VanSteen-algorithm [1]. 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.