OBJECTIVES Combining the analysis of family-based samples with unrelated individuals can enhance the power of genetic association studies. Various combined analysis techniques have been recently developed; as yet, there have been no comparisons of their power, or robustness to confounding factors. We investigated empirically the power of up to six combined methods using simulated samples of tri...

Motivated by examples from genetic association studies, this article considers the model selection problem in a general complex linear model system and in a Bayesian framework. We discuss formulating model selection problems and incorporating context-dependent a priori information through different levels of prior specifications. We also derive analytic Bayes factors and their approximations to...

Motivated by the challenges associated with accounting for the ascertainment when analyzing secondary phenotypes that are correlated with case-control status, Lin and Zeng have proposed a method that properly reflects the case-control sampling (Lin and Zeng, 2009). The Lin and Zeng method has the advantage of accurately estimating effect sizes for secondary phenotypes that are normally distribu...

BACKGROUND The variance explained by genetic variants as identified in (genome-wide) genetic association studies is typically small compared to family-based heritability estimates. Explanations of this 'missing heritability' have been mainly genetic, such as genetic heterogeneity and complex (epi-)genetic mechanisms. METHODOLOGY We used comprehensive simulation studies to show that three phen...

Meta-analysis has become a popular tool for genetic association studies to combine different genetic studies. A key challenge in meta-analysis is heterogeneity, or the differences in effect sizes between studies. Heterogeneity complicates the interpretation of meta-analyses. In this paper, we describe ForestPMPlot, a flexible visualization tool for analyzing studies included in a meta-analysis....

The use of genetically isolated populations can empower next-generation association studies. In this review, we discuss the advantages of this approach and review study design and analytical considerations of genetic association studies focusing on isolates. We cite successful examples of using population isolates in association studies and outline potential ways forward.

OBJECTIVE In studies of associations between genetic factors and outcomes where change in phenotype is of interest, proper modeling of the data, particularly the treatment of baseline trait values, is required to draw valid conclusions. METHODS The authors compared models of blood pressure response to a cold pressor test with and without inclusion of baseline blood pressure as a regressor and...

Gene-environment interactions are of interest in genetic association studies for several reasons. First, the power to detect genetic effects may be substantially decreased if those effects differ according to environmental exposure and if no account is taken of this interaction with environmental exposure in the analysis. Second, such interactions may indicate a phenomenon of genuine biological...