Table 1 Summary of the features, the pros and cons of the different type of methods described in this review and the software currently available
From: The impact of rare and low-frequency genetic variants in common disease
Type of method | Methods | Main features | Ability to discriminate risk and protective alleles | Range of study designs they can be applied to | Allelic architecture scenarios the method is compatible with | Available software |
|---|---|---|---|---|---|---|
Burden test | ARIEL test [53], RWAS [54], CAST [55], CMC method [56], MZ Test [57], WSS [58], aSum [59], Step-up [60], EREC test [61], VT [62], KBAC method [63], RBT [64] | Collapsing genetic variants into a single score, assumption that tested variants are all causal and associated with the trait with the same direction and magnitude of effect | No | Causal variants, e.g. loss of function (LoF) variants | All variants have the same direction and magnitude of effect | ARIEL, EPACTS, GRANVIL, PLINK/SEQ, Rvtests, SCORE-Seq, SKAT, VAT, KBAC, RAREMETAL |
Variance-component test | Allowing for both risk and protective alleles, i.e. tested variants can have different directions of effect | Yes | Applicable to all available variants, possibly using some weighting strategy | Variants can have opposing directions of effect | EPACTS, PLINK/SEQ, SCORE-Seq, SKAT, VAT, RAREMETAL | |
Combined test | Combining results from two or more complementary tests | Yes | Applicable to all available variants, possibly using some weighting strategy | Variants can have both opposing or same direction of effect | EPACTS, PLINK/SEQ, MiST, SKAT, RAREMETAL | |
Other tests | Accounting for signal sparsity | No | Applicable to all available variants, possibly using some weighting strategy | Variants are sparse | MENDEL |