Document Detail

Methods for investigating gene-environment interactions in candidate pathway and genome-wide association studies.
MedLine Citation:
PMID:  20070199     Owner:  NLM     Status:  MEDLINE    
Despite the considerable enthusiasm about the yield of novel and replicated discoveries of genetic associations from the new generation of genome-wide association studies (GWAS), the proportion of the heritability of most complex diseases that have been studied to date remains small. Some of this "dark matter" could be due to gene-environment (G x E) interactions or more complex pathways involving multiple genes and exposures. We review the basic epidemiologic study design and statistical analysis approaches to studying G x E interactions individually and then consider more comprehensive approaches to studying entire pathways or GWAS data. In addition to the usual issues in genetic association studies, particular care is needed in exposure assessment, and very large sample sizes are required. Although hypothesis-driven, pathway-based and agnostic GWA study approaches are generally viewed as opposite poles, we suggest that the two can be usefully married using hierarchical modeling strategies that exploit external pathway knowledge in mining genome-wide data.
Duncan Thomas
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Annual review of public health     Volume:  31     ISSN:  1545-2093     ISO Abbreviation:  Annu Rev Public Health     Publication Date:  2010  
Date Detail:
Created Date:  2010-03-18     Completed Date:  2010-06-25     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  8006431     Medline TA:  Annu Rev Public Health     Country:  United States    
Other Details:
Languages:  eng     Pagination:  21-36     Citation Subset:  IM    
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MeSH Terms
Bayes Theorem
Environmental Exposure / adverse effects*
Genetic Predisposition to Disease*
Genome-Wide Association Study / methods*
Models, Theoretical
Public Health
Research Design
Grant Support
Comment In:
Annu Rev Public Health. 2010;31:1-8   [PMID:  20001819 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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