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\item Suitable for effects in one direction.   \item High power to detect the association between rare variants and disease trait \cite{Price_2010}.  \end{itemize}  \item C-alpha \cite{Neale_2011}: Test the variance of the effect size foracross rare  variants in a specific genomic window  (No effect, increase or decrease risk). \begin{itemize}  \item Sensitive to risk and protective variants in the same gene.  \item Powerful when the effects are in different directions directions.  \end{itemize}  \end{itemize}  \item Joint-modeling method