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\begin{itemize}  \item Sensitive to risk and protective variants in the same gene.  \item Powerful when the effects are in different directions.  \item R package: SKAT\cite{lee2014skat}  \end{itemize}  \end{itemize}  \item Joint-modeling method 
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\begin{itemize}  \item Particularly useful when number of predictors exceeds the number of observations.  \item We select phenotype associated SNVs via elastic-net regularization from the 100 bootstrap samples.  \item We performed analysis with R package glmnet \cite{Friedman_2010} \cite{Friedman_2010, Simon_2011, Tibshirani_2011a}  \end{itemize}  \end{itemize}  \item Tree-Based method