Epistasis Blog

From the Computational Genetics Laboratory at the University of Pennsylvania (www.epistasis.org)

Tuesday, April 05, 2005

Genome-wide strategies for detecting epistasis

A wonderful new paper in Nature Genetics explores the plausibility of detecting epistasis in genome-wide assocation studies. Here is the citation and the abstract:

Marchini J, Donnelly P, Cardon LR. Genome-wide strategies for detecting multiple loci that influence complex diseases. Nat Genet. 2005 Apr;37(4):413-7. [PubMed]

After nearly 10 years of intense academic and commercial research effort, large genome-wide association studies for common complex diseases are now imminent. Although these conditions involve a complex relationship between genotype and phenotype, including interactions between unlinked loci, the prevailing strategies for analysis of such studies focus on the locus-by-locus paradigm. Here we consider analytical methods that explicitly look for statistical interactions between loci. We show first that they are computationally feasible, even for studies of hundreds of thousands of loci, and second that even with a conservative correction for multiple testing, they can be more powerful than traditional analyses under a range of models for interlocus interactions. We also show that plausible variations across populations in allele frequencies among interacting loci can markedly affect the power to detect their marginal effects, which may account in part for the well-known difficulties in replicating association results. These results suggest that searching for interactions among genetic loci can be fruitfully incorporated into analysis strategies for genome-wide association studies.

See also the News and Views piece about the paper:

Daly MJ, Altshuler D. Partners in crime. Nat Genet. 2005 Apr;37(4):337-8. [PubMed]

The genetic culprits that contribute to common diseases remain at large, despite dedicated sleuthing by many laboratories. A new study evaluates the power of genome-wide searches for variants acting in combination, with results that are both unexpected and encouraging.

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