Some methods, such as genetic burden tests, have been specifically developed to study genetic association of rare variants. These methods aggregate rare variants over genetic regions, such as genes or whole pathways, and evaluate cumulative effects of multiple genetic variants. These methods may increase power when multiple variants in the region are associated with a disease or a trait. In addition, compared to a
genome-wide association study, a region or gene based test performs much fewer tests resulting in a less stringent multiple-hypothesis correction than the
genome-wide significance. Some examples of these methods are SKAT, SKAT-O, aSUM and STAAR.
SNP annotations help to prioritize rare functional variants, and incorporating these annotations can effectively boost the power of genetic association of rare variants analysis of
whole exome and
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