Gene-environment interaction and affected sib pair linkage analysis. Gauderman, W., J. & Siegmund, K., D. Hum Hered, 52(1):34-46., 2001.
abstract   bibtex   
OBJECTIVES: Gene-environment (GxE) interaction influences risk for many complex disease traits. However, genome screens using affected sib pair linkage techniques are typically conducted without regard for GxE interaction. We propose a simple extension of the commonly used mean test and evaluate its power for several forms of GxE interaction. METHODS: We compute expected IBD sharing by sibling exposure profile, that is by whether two sibs are exposed (EE), unexposed (UU), or are discordant for exposure (EU). We describe a simple extension of the mean test, the "mean-interaction" test that utilizes heterogeneity in IBD sharing across EE, EU, and UU sib pairs in a test for linkage. RESULTS: The mean-interaction test provides greater power than the mean test for detecting linkage in the presence of moderate or strong GxE interaction, typically when the interaction relative risk (R(ge)) exceeds 3 or is less than 1/3. In the presence of strong interaction (R(ge) = 10), the required number of affected sib pairs to achieve 80% power for detecting linkage is approximately 30% higher when the environmental factor is ignored in the mean test, than when it is utilized in the mean-interaction test. CONCLUSION: Linkage methods that incorporate environmental data and allow for interaction can lead to increased power for localizing a disease gene involved in a GxE interaction.
@article{
 title = {Gene-environment interaction and affected sib pair linkage analysis},
 type = {article},
 year = {2001},
 identifiers = {[object Object]},
 keywords = {*Genetic Techniques,*Statistics,Chromosome Mapping/methods,Chromosomes, Human,Computer Simulation,Environment,Family Characteristics,Human,Linkage (Genetics)/*genetics,Models, Genetic,Models, Statistical,Research Design,Sample Size,Software,Support, U.S. Gov't, P.H.S.},
 pages = {34-46.},
 volume = {52},
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 abstract = {OBJECTIVES: Gene-environment (GxE) interaction influences risk for many complex disease traits. However, genome screens using affected sib pair linkage techniques are typically conducted without regard for GxE interaction. We propose a simple extension of the commonly used mean test and evaluate its power for several forms of GxE interaction. METHODS: We compute expected IBD sharing by sibling exposure profile, that is by whether two sibs are exposed (EE), unexposed (UU), or are discordant for exposure (EU). We describe a simple extension of the mean test, the "mean-interaction" test that utilizes heterogeneity in IBD sharing across EE, EU, and UU sib pairs in a test for linkage. RESULTS: The mean-interaction test provides greater power than the mean test for detecting linkage in the presence of moderate or strong GxE interaction, typically when the interaction relative risk (R(ge)) exceeds 3 or is less than 1/3. In the presence of strong interaction (R(ge) = 10), the required number of affected sib pairs to achieve 80% power for detecting linkage is approximately 30% higher when the environmental factor is ignored in the mean test, than when it is utilized in the mean-interaction test. CONCLUSION: Linkage methods that incorporate environmental data and allow for interaction can lead to increased power for localizing a disease gene involved in a GxE interaction.},
 bibtype = {article},
 author = {Gauderman, W J and Siegmund, K D},
 journal = {Hum Hered},
 number = {1}
}

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