Objective: To determine whether accounting for gene-environment (G×E) interactions improves the power to detect associations between rare variants and a disease, we have extended three statistical methods and compared their power under various simulated disease models. Methods: To test for association of a group of rare variants with a disease, Min-P uses the lowest p value within the group of variants, CAST (Cohort Allelic Sums Test) uses an indicator variable to quantify the rare alleles within the group of variants, and SKAT (Sequence Kernel Association Test) uses a logistic regression based on kernel machine. For each method, we incorporate a term for the G×E interaction and test for association and interaction jointly. Results: When testing for disease association with a set of rare variants, accounting for G×E interactions can improve power in specific situations (pure interaction or high proportion of causal variants interacting with the environment). However, the power of this approach can decrease, in particular in the presence of main genetic or environmental effects. Among the methods compared, the optimized and weighted SKAT performed best, whether to test for genetic association or to test it jointly with G×E interactions. Conclusion: This approach can be used in specific situations but is not appropriate for a primary analysis.
© 2013 S. Karger AG, Basel
- Rare variant
- Gene-environment interaction
- Case-control design
- Logistic regression
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John S. Witte, PhD
MC 3110, UCSF, Helen Diller Family Cancer Research Building
1450 3rd Street, PO Box 589001
San Francisco, CA 94158-9001 (USA)
Published online: April 11, 2013
Number of Print Pages : 10
Number of Figures : 2, Number of Tables : 2, Number of References : 34
Additional supplementary material is available online - Number of Parts : 1
Human Heredity (International Journal of Human and Medical Genetics)
Vol. 74, No. 3-4, Year 2012 (Cover Date: April 2013)
Journal Editor: Clerget-Darpoux F. (Paris)
ISSN: 0001-5652 (Print), eISSN: 1423-0062 (Online)
For additional information: http://www.karger.com/HHE
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