Source:http://linkedlifedata.com/resource/pubmed/id/21308767
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2011-3-11
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pubmed:abstractText |
Many complex diseases are likely to be a result of the interplay of genes and environmental exposures. The standard analysis in a genome-wide association study (GWAS) scans for main effects and ignores the potentially useful information in the available exposure data. Two recently proposed methods that exploit environmental exposure information involve a two-step analysis aimed at prioritizing the large number of SNPs tested to highlight those most likely to be involved in a GE interaction. For example, Murcray et al. ([2009] Am J Epidemiol 169:219–226) proposed screening on a test that models the G-E association induced by an interaction in the combined case-control sample. Alternatively, Kooperberg and LeBlanc ([2008] Genet Epidemiol 32:255–263) suggested screening on genetic marginal effects. In both methods, SNPs that pass the respective screening step at a pre-specified significance threshold are followed up with a formal test of interaction in the second step. We propose a hybrid method that combines these two screening approaches by allocating a proportion of the overall genomewide significance level to each test. We show that the Murcray et al. approach is often the most efficient method, but that the hybrid approach is a powerful and robust method for nearly any underlying model. As an example, for a GWAS of 1 million markers including a single true disease SNP with minor allele frequency of 0.15, and a binary exposure with prevalence 0.3, the Murcray, Kooperberg and hybrid methods are 1.90, 1.27, and 1.87 times as efficient, respectively, as the traditional case-control analysis to detect an interaction effect size of 2.0.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/1RC2HL101651,
http://linkedlifedata.com/resource/pubmed/grant/P30CA014089,
http://linkedlifedata.com/resource/pubmed/grant/P30ES007048,
http://linkedlifedata.com/resource/pubmed/grant/R01ES016813,
http://linkedlifedata.com/resource/pubmed/grant/R01HL087680,
http://linkedlifedata.com/resource/pubmed/grant/R41CA141852,
http://linkedlifedata.com/resource/pubmed/grant/RC2 HL101651-02,
http://linkedlifedata.com/resource/pubmed/grant/T32ES013678,
http://linkedlifedata.com/resource/pubmed/grant/U01 ES015090-03,
http://linkedlifedata.com/resource/pubmed/grant/U01 HG005927-01,
http://linkedlifedata.com/resource/pubmed/grant/U01ES015090,
http://linkedlifedata.com/resource/pubmed/grant/U01HG005927
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
1098-2272
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
201-10
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pubmed:dateRevised |
2011-9-26
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pubmed:meshHeading |
pubmed-meshheading:21308767-Case-Control Studies,
pubmed-meshheading:21308767-Disease,
pubmed-meshheading:21308767-Environment,
pubmed-meshheading:21308767-Genome-Wide Association Study,
pubmed-meshheading:21308767-Humans,
pubmed-meshheading:21308767-Logistic Models,
pubmed-meshheading:21308767-Models, Genetic,
pubmed-meshheading:21308767-Molecular Epidemiology,
pubmed-meshheading:21308767-Polymorphism, Single Nucleotide,
pubmed-meshheading:21308767-Sample Size,
pubmed-meshheading:21308767-Software
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pubmed:year |
2011
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pubmed:articleTitle |
Sample size requirements to detect gene-environment interactions in genome-wide association studies.
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pubmed:affiliation |
Department of Preventive Medicine, University of Southern California, Los Angeles, California 90089-9010, USA. Murcray@usc.edu
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pubmed:publicationType |
Journal Article,
Comparative Study,
Comment,
Evaluation Studies,
Research Support, N.I.H., Extramural
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