Table 3.
Rare variant association methods.
| Method | First author, reference | Protective | Pooling | Implementation |
|---|---|---|---|---|
| DMAF | Brisbin | Y | Subjects | |
| CMC | Li (Li and Leal, 2008) | N | SNVs, then Subjects | SNVs with MAF ≤ 0.01 collapsed (default); variants with MAF > 0.01 analyzed with Hotelling T2 |
| RVT1 | Morris (Morris and Zeggini, 2010) | N | SNVs | Logistic regression |
| KBAC | Liu (Liu and Leal, 2010) | N | SNVs | Default |
| WSS | Madsen (Madsen and Browning, 2009) | N | SNVs | Empirical p-value from 500 permutations |
| VT | Price (Price et al., 2010) | N | SNVs | 10,000 permutations, variant weights = 1 |
| Hotel | Hotelling (Hotelling, 1931), Xiong (Xiong et al., 2002) | Y | Subjects | Blocks of 10 SNVs were analyzed with manova, combined with Fisher’s method |
| aSum | Han (Han and Pan, 2010) | Y | SNVs | Empirical p-value from 500 permutations; α0 = 0.1 (default) |
| C-alpha | Neale (Neale et al., 2011) | Y | Subjects | Empirical p-value from 500 permutations; singletons pooled |
“Protective” column indicates whether the method is designed to accommodate protective variants; “pooling” indicates the dimension across which information is pooled.