Combining Disease Models to Test for Gene–Environment Interaction in Nuclear Families
Article first published online: 14 MAR 2011
© 2011, The International Biometric Society
Volume 67, Issue 4, pages 1260–1270, December 2011
How to Cite
Hoffmann, T. J., Vansteelandt, S., Lange, C., Silverman, E. K., DeMeo, D. L. and Laird, N. M. (2011), Combining Disease Models to Test for Gene–Environment Interaction in Nuclear Families. Biometrics, 67: 1260–1270. doi: 10.1111/j.1541-0420.2011.01581.x
- Issue published online: 14 DEC 2011
- Article first published online: 14 MAR 2011
- Received July 2009. Revised December 2010. Accepted December 2010.
- Binary trait;
- Candidate gene analysis;
- Family-based association tests;
- Gene–environment interaction;
Summary It is useful to have robust gene–environment interaction tests that can utilize a variety of family structures in an efficient way. This article focuses on tests for gene–environment interaction in the presence of main genetic and environmental effects. The objective is to develop powerful tests that can combine trio data with parental genotypes and discordant sibships when parents' genotypes are missing. We first make a modest improvement on a method for discordant sibs (discordant on phenotype), but the approach does not allow one to use families when all offspring are affected, e.g., trios. We then make a modest improvement on a Mendelian transmission-based approach that is inefficient when discordant sibs are available, but can be applied to any nuclear family. Finally, we propose a hybrid approach that utilizes the most efficient method for a specific family type, then combines over families. We utilize this hybrid approach to analyze a chronic obstructive pulmonary disorder dataset to test for gene–environment interaction in the Serpine2 gene with smoking. The methods are freely available in the R package fbati.