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Abstract Details
Activity Number:
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441
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Type:
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Invited
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Date/Time:
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Wednesday, August 3, 2011 : 8:30 AM to 10:20 AM
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Sponsor:
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Section on Statistics in Epidemiology
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Abstract - #300410 |
Title:
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Assessing GxE Using Nuclear Families: Can We Make It Robust?
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Author(s):
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Clarice Weinberg*+ and Min Shi and David Umbach
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Companies:
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National Institute of Environmental Health Sciences and National Institute of Environmental Health Sciences and National Institute of Environmental Health Sciences
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Address:
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P.O. Box 12233, Research Triangle Park, NC, 27709, USA
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Keywords:
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case-only ;
family-based analysis ;
gene-by-environment interaction ;
environment
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Abstract:
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Complex diseases arise through joint action of environmental factors and genetic susceptibility variants. Investigators have assumed that the robustness protecting family-based genotype analyses from bias due to population stratification will protect assessments of interaction. Not true. When testing against a multiplicative joint effects model, the case-only design offers good power, but is invalid if G and E are correlated in the source population. Four mechanisms can produce G/E dependence: 1. Subpopulations vary in both ancestry and cultural traditions; 2. Family history influences behavior through avoidance of exposures perceived as risky; 3. G influences E; or 4. Selective attrition produces correlation in older age strata. We propose a sibling-augmented case-only approach, which is robust against the first two mechanisms, and is therefore valid when a young-onset disease is studied and G does not influence E. With this design an unaffected sibling is randomly selected and exposure ascertained for that sibling. The case is genotyped if the case-control pair is exposure-discordant. A logistic model permits testing of the exposure main effect and GxE interaction.
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