TY - JOUR
T1 - You've Gotta Be Lucky
T2 - Coverage and the elusive gene-gene interaction
AU - Reimherr, Matthew
AU - Nicolae, Dan L.
PY - 2011/1
Y1 - 2011/1
N2 - 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.
AB - 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.
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U2 - 10.1111/j.1469-1809.2010.00615.x
DO - 10.1111/j.1469-1809.2010.00615.x
M3 - Article
C2 - 20977438
AN - SCOPUS:78650150425
SN - 0003-4800
VL - 75
SP - 105
EP - 111
JO - Annals of Human Genetics
JF - Annals of Human Genetics
IS - 1
ER -