Rare variant tests
Summary of rare variant tests for sequence data
Compiled by Cristen Willer and Suzanne Leal for the ESP Feb 1, 2011
* indicates applicability to quantitative data
? indicates possible applicability to quantitative data with adaptation Blue font indicates implementation in upcoming PLINKSeq release (http://atgu.mgh.harvard.edu/plinkseq/)
Will be implemented in PlinkSeq
1) Aggregate tests using a cut off e.g. 1 % analyzing nonsynonymous variants to detect detrimental variants
| Test Name | Reference | Software | Notes |
|---|---|---|---|
| CMC/T1 test* | Li & Leal, 2008 | ||
| KBAC | Liu & Leal, 2010 | ||
| VT* | Price et al., 2010 | http://genetics.bwh.harvard.edu/rare_variants/ | |
| WSS | Madsen & Browning, 2009 | ||
| CMAT | Zawistowski et al. 2010 | ||
| ANRV/GRANVIL* | Morris & Zeggini | ||
| RARECOVER | Bhati et al. 2010 | ||
| CCRaVAT and QuTie* | Lawrence et al. 2010 | http://www.sanger.ac.uk/resources/software/rarevariant/ | |
| RVE (rare variant exclusive) | Cohen & Hobb |
2) Aggregate tests for protective and detrimental variants (recommend 1% cutoff)
| Test Name | Reference | Software | Notes |
|---|---|---|---|
| C-alpha | [Neale et al., submitted] | ||
| Ionita-Laza & Lange | Ionita-Laza & Lange, 2011 | ||
| DASH* | Han & Pan | ||
| SKAT* | Wu et al., 2010 | http://www.hsph.harvard.edu/~xlin/software.html | |
| WHaIT | Li et al. 2010 | http://www.sph.umich.edu/csg/yli/whait/ | |
| EMMPAT* | King et al. 2010 | http://home.uchicago.edu/~crk8e/papersup.html |
3) Analyzing common and rare variants together (could down-weight or threshold common variants)
| Test Name | Reference | Software | Notes |
|---|---|---|---|
| WSS | Madsen & Browning, 2009 | ||
| RARECOVER | Bhati et al. 2010 | ||
| Step-Up Collapsing* | Hoffman et al. 2010 | ||
| CMC/T5 test* | Li & Leal, 2008 | ||
| MENDEL* | Zhou et al. 2011 | http://www.genetics.ucla.edu/software/download?package=1 |
4.) Analyze higher frequency rare variants >1% individually
Use same regression frame work which has been used for common variants*
Use meta analysis to combine results from sequence data and imputed genotypes to increase power*
Additional tests
Test Name Notes Reference Website/Code
Logic Regression* Kooperberg et al. (2001)
http://kooperberg.fhcrc.org/papers/2001gaw.pdf
Sequence diversity Anderson (2006)
Sequence dissimilarity* Schork et al. (2008), Wessel et al. (2006)
Ridge Regression* Malo et al. (2008)
Additional tests
| Test Name | Reference | Software | Notes |
|---|---|---|---|
| Logic regression* | Kooperberg et al. 2001 | ||
| Sequence diversity | Anderson et al. 2006 | ||
| Sequence dissimilarity* | Schork et al. 2008, Wessel et al. 2006 | ||
| Ridge regression * | Malo et al. 2008 |
