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You've Gotta Be Lucky: Coverage and the Elusive Gene–Gene Interaction

You've Gotta Be Lucky: Coverage and the Elusive Gene–Gene Interaction Genome‐wide association studies (GWAS) have led to a large number of single‐SNP association findings, but there has been, so far, no investigation resulting in the discovery of a replicable gene–gene interaction. In this paper, we examine some of the possible explanations for the lack of findings, and argue that coverage of causal variation not only has a large effect on the loss in power, but that the effect is larger than in the single‐SNP analyses. We show that the product of linkage disequilibrium measures, r2, between causal and tested SNPs offers a good approximation to the loss in efficiency as defined by the ratio of sample sizes that lead to similar power. We also demonstrate that, in addition to the huge search space, the loss in power due to coverage when using commercially available platforms makes the search for gene–gene interactions daunting. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Human Genetics Wiley

You've Gotta Be Lucky: Coverage and the Elusive Gene–Gene Interaction

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References (16)

Publisher
Wiley
Copyright
Copyright © 2011 Wiley Subscription Services
ISSN
0003-4800
eISSN
1469-1809
DOI
10.1111/j.1469-1809.2010.00615.x
pmid
20977438
Publisher site
See Article on Publisher Site

Abstract

Genome‐wide association studies (GWAS) have led to a large number of single‐SNP association findings, but there has been, so far, no investigation resulting in the discovery of a replicable gene–gene interaction. In this paper, we examine some of the possible explanations for the lack of findings, and argue that coverage of causal variation not only has a large effect on the loss in power, but that the effect is larger than in the single‐SNP analyses. We show that the product of linkage disequilibrium measures, r2, between causal and tested SNPs offers a good approximation to the loss in efficiency as defined by the ratio of sample sizes that lead to similar power. We also demonstrate that, in addition to the huge search space, the loss in power due to coverage when using commercially available platforms makes the search for gene–gene interactions daunting.

Journal

Annals of Human GeneticsWiley

Published: Jan 1, 2011

Keywords: ; ; ;

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