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Ma, J.Z.* ; Xiao, F.F.* ; Xiong, M.* ; Andrew, A.S.* ; Brenner, H.* ; Duell, E.J.* ; Haugen, A.* ; Hoggart, C.* ; Hung, R.J.* ; Lazarus, P.* ; Liu, C.L.* ; Matsuo, K.* ; Mayordomok, J.I.* ; Schwartz, A.G.* ; Staratschek-Jox, A.* ; Wichmann, H.-E. ; Yang, P.* ; Amos, C.I.*

Natural and orthogonal interaction framework for modeling gene-environment interactions with application to lung cancer.

Hum. Hered. 73, 185-194 (2012)

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Open Access Green as soon as Postprint is submitted to ZB.

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Objectives: We aimed at extending the Natural and Orthogonal Interaction (NOIA) framework, developed for modeling gene-gene interactions in the analysis of quantitative traits, to allow for reduced genetic models, dichotomous traits, and gene-environment interactions. We evaluate the performance of the NOIA statistical models using simulated data and lung cancer data. Methods: The NOIA statistical models are developed for additive, dominant, and recessive genetic models as well as for a binary environmental exposure. Using the Kronecker product rule, a NOIA statistical model is built to model gene-environment interactions. By treating the genotypic values as the logarithm of odds, the NOIA statistical models are extended to the analysis of case-control data. Results: Our simulations showed that power for testing associations while allowing for interaction using the NOIA statistical model is much higher than using functional models for most of the scenarios we simulated. When applied to lung cancer data, much smaller p values were obtained using the NOIA statistical model for either the main effects or the SNP-smoking interactions for some of the SNPs tested. Conclusion: The NOIA statistical models are usually more powerful than the functional models in detecting main effects and interaction effects for both quantitative traits and binary traits.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Statistical Power ; Genetic Association Studies ; Case-control Association Analysis ; Gene-environment Interaction Environmental Risk Factor ; Association Mapping ; Orthogonal Modeling; GENOME-WIDE ASSOCIATION; MISSING HERITABILITY; LOCI

ISSN (print) / ISBN 0001-5652

e-ISSN 1423-0062

Journal Human Heredity

Quellenangaben Volume: 73, Issue: 4, Pages: 185-194

Publisher Karger

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology (EPI)