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  \item Brief literature review:   \begin{itemize}  \item Most genetic association studies focus on common variants which are effective for common disease caused by common variants.  \item Rare genetic variants can play major roles in influencing complex traits. \cite{Pritchard_2001, Schork_2009}  \item The rare susceptibility variants identified through sequencing have potential to explain some of the 'missing heritability' of complex traits. \cite{Eichler_2010}.  \item However, standard methods to test for association with single genetic variants are underpowered for rare variants unless sample sizes are very large. \cite{Lee_2014}