Statistical Considerations in the Analysis of Rare Variants

Recently, whole-genome and whole-exome sequencing has begun to demonstrate success in the identification of disease-causing genes. Many of these genes exhibit abnormal genetic behavior and low prevalence in the population; these molecules are commonly referred to as rare variants. In this chapter, we provide an overview of rare variants and their scientific relevance in medicine and public health. We then provide a review of existing methods for association, primarily focusing on the sequence kernel association test (SKAT) and related methods. These procedures are related to kernel machines, which we will also describe. Finally, we discuss the implications of rare variants in terms of multiple testing.

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