Testing for direct genetic effects using a screening step in family-based association studies
Lutz, Sharon M.
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CitationLutz, Sharon M., Stijn Vansteelandt, and Christoph Lange. 2013. “Testing for direct genetic effects using a screening step in family-based association studies.” Frontiers in Genetics 4 (1): 243. doi:10.3389/fgene.2013.00243. http://dx.doi.org/10.3389/fgene.2013.00243.
AbstractIn 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.
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