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## RAREMETAL METHOD

, 23:52, 8 April 2014
VT META ANALYSIS
Including variants that are not associated to phenotype can hurt power. Variable threshold test is designed to choose the optimal allele frequency threshold amongst rare variants in a gene, to gain power. The test statistic is defined as the maximum burden score statistic calculated using every possible frequency threshold
$T_{VT}=\max(T_{b\left(f_1\right)},T_{b\left(f_2\right)},\dots,T_{b\left(f_m\right)})$,
where the burden test statistic under any allele frequency threshold can be constructed from single variant meta-analysis statistics using
$T_{b\left(f_j\right)}=\boldsymbol{\phi}_{f_j}^\mathbf{T}\mathbf{U_{meta}}\bigg/\sqrt{\boldsymbol{\phi}_{f_j}^\mathbf{T}\mathbf{V_{meta}}\boldsymbol{\phi}_{f_j}}$,
where $j$ represents any allele frequency in a group of rare variants, $\boldsymbol{\phi}_{f_j}$ is a vector of 0 and 1, indicating if a variant is included in the analysis using frequency threshold <mat>f_i [/itex]
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