Back to Search
Start Over
A Sibling-augmented Case-only Approach for Assessing Multiplicative Gene-Environment Interactions.
- Source :
-
American Journal of Epidemiology . Nov2011, Vol. 174 Issue 10, p1183-1189. 7p. - Publication Year :
- 2011
-
Abstract
- Family-based designs protect analyses of genetic effects from bias that is due to population stratification. Investigators have assumed that this robustness extends to assessments of gene-environment interaction. Unfortunately, this assumption fails for the common scenario in which the genotyped variant is related to risk through linkage with a causative allele. Bias also plagues other methods of assessment of gene-environment interaction. When testing against multiplicative joint effects, the case-only design offers excellent power, but it is invalid if genotype and exposure are correlated in the population. The authors describe 4 mechanisms that produce genotype-exposure dependence: exposure-related genetic population stratification, effects of family history on behavior, genotype effects on exposure, and selective attrition. They propose a sibling-augmented case-only (SACO) design that protects against the former 2 mechanisms and is therefore valid for studying young-onset disease in which genotype does not influence exposure. A SACO design allows the ascertainment of genotype and exposure for cases and exposure for 1 or more unaffected siblings selected randomly. Conditional logistic regression permits assessment of exposure effects and gene-environment interactions. Via simulations, the authors compare the likelihood-based inference on interactions using the SACO design with that based on other designs. They also show that robust analyses of interactions using tetrads or disease-discordant sibling pairs are equivalent to analyses using the SACO design. [ABSTRACT FROM PUBLISHER]
Details
- Language :
- English
- ISSN :
- 00029262
- Volume :
- 174
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- American Journal of Epidemiology
- Publication Type :
- Academic Journal
- Accession number :
- 67133625
- Full Text :
- https://doi.org/10.1093/aje/kwr231