With the development of next-generation sequencing technology, there is a great demand for powerful statistical methods to detect rare variants (minor allele frequencies (MAFs)-MidPmethod (Cheung et al., 2012, Genet Epidemiol 36: 675–685) and propose an approach (named ‘adaptive combination of P-values for rare variant association testing’, abbreviated as ‘ADA’) that adaptively combines per-site P-values with the weights based on MAFs. Before combining P-values, we first imposed a truncation threshold upon the per-site P-values, to guard against the noise caused by the inclusion of neutral variants. ThisADA method is shown to outperform popular burden tests and non-burden tests under many scenarios. ADA is recommended for next-generation sequencing data analysis where many neutral variants may be included in a functional region.
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