Rare Variant Association Testing for Next-Generation Sequencing Data via Hierarchical Clustering

It is thought that a proportion of the genetic susceptibility to complex diseases is due to low-frequency and rare variants. Next-generation sequencing in large populations facilitates the detection of rare variant associations to disease risk. In order to achieve adequate power to detect association at low-frequency and rare variants, locus-specific statistical methods are being developed that combine information across variants within a functional unit and test for association with this enriched signal through so-called burden tests.