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

View 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.

Investigators
Abbreviation
Front Genet
Publication Date
2013-11-21
Volume
4
Page Numbers
243
Pubmed ID
24312120
Medium
Electronic-eCollection
Full Title
Testing for direct genetic effects using a screening step in family-based association studies.
Authors
Lutz SM, Vansteelandt S, Lange C