AUTHOR=Lutz Sharon M., Vansteelandt Stijn , Lange Christoph 

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

JOURNAL=Frontiers in Genetics

VOLUME=Volume 4 - 2013

YEAR=2013

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2013.00243

DOI=10.3389/fgene.2013.00243

ISSN=1664-8021

ABSTRACT=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.