Association Analysis for Rare Variants
Statistical analysis strategies for association studies involving rare variants.
Bansal V, Libiger O, Torkamani A, Schork NJ.
Nat Rev Genet. 2010 Nov;11(11):773-85. Epub 2010 Oct 13. Review.
PMID: 20940738 http://www.ncbi.nlm.nih.gov/sites/entrez/20940738- focused on single nucleotide rare variants
links to > 10 association tests at the gene or genomic area level, with correction or subpopulation and covariates
- quite of an effort to understand and follow up on all the methods referenced
- briefly mentions pathway analysis (ref to Autism Nature paper)
An evaluation of statistical approaches to rare variant analysis in genetic association studies.
Morris AP, Zeggini E.
Genet Epidemiol. 2010 Feb;34(2):188-93.
PMID: 19810025
Gene-set Association Tests for Rare Variants
Similar Gene-set Analysis Strategies for Genetics Data
Cancer Mutations
Patient-oriented gene set analysis for cancer mutation data
Boca SM, Kinzler K, Velculescu VE, Vogelstein B, Parmigiani G.
Genome Biol. 2010 Nov 23;11(11):R112.
PMID: 21092299 http://www.ncbi.nlm.nih.gov/sites/entrez/21092299- It's basically the same idea applied to cancer instead of autism.
- However, lacking the control patients (since cancer is high mutation frequency, that would not make sense), they have to define the null hypothesis using randomly placed mutations.
- What they call "exclusivity principle" is what I usually call the "OR combination logic" (i.e. at least one perturbed gene for the pathway/gene-set to be perturbed).
Other paper to look at
Functional genomics complements quantitative genetics in identifying disease-gene associations.
Guan Y, Ackert-Bicknell CL, Kell B, Troyanskaya OG, Hibbs MA.
PLoS Comput Biol. 2010 Nov 11;6(11):e1000991
http://www.ncbi.nlm.nih.gov/pubmed/21085640