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The objective of this paper is to discuss and develop alternative computational methods to accurately and efficiently calculate significance P‐values for the commonly used sequence kernel association test (SKAT) and adaptive sum of SKAT and burden test (SKAT‐O) for variant set association. We show that the existing software can lead to either conservative or inflated type I errors. We develop alternative...
Recent sequencing efforts have focused on exploring the influence of rare variants on the complex diseases. Gene level based tests by aggregating information across rare variants within a gene have become attractive to enrich the rare variant association signal. Among them, the sequence kernel association test (SKAT) has proved to be a very powerful method for jointly testing multiple rare variants...
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