title: Incorporating gene-environment interaction in testing for association with rare genetic variants.
abstract: OBJECTIVE
  The incorporation of gene-environment interactions could improve the ability to detect genetic associations with complex traits. For common genetic variants, single-marker interaction tests and joint tests of genetic main effects and gene-environment interaction have been well-established and used to identify novel association loci for complex diseases and continuous traits. For rare genetic variants, however, single-marker tests are severely underpowered due to the low minor allele frequency, and only a few gene-environment interaction tests have been developed. We aimed at developing powerful and computationally efficient tests for gene-environment interaction with rare variants.
  
  
  METHODS
  In this paper, we propose interaction and joint tests for testing gene-environment interaction of rare genetic variants. Our approach is a generalization of existing gene-environment interaction tests for multiple genetic variants under certain conditions.
  
  
  RESULTS
  We show in our simulation studies that our interaction and joint tests have correct type I errors, and that the joint test is a powerful approach for testing genetic association, allowing for gene-environment interaction. We also illustrate our approach in a real data example from the Framingham Heart Study.
  
  
  CONCLUSIONS
  Our approach can be applied to both binary and continuous traits, it is powerful and computationally efficient.
authors: Department of Biostatistics, Boston University School of Public Health, Boston, Mass., USA.
authors: Han
authors: H
authors: Chen
authors: James B
authors: JB
authors: Meigs
authors: Josée
authors: J
authors: Dupuis
mesh_terms: D001786:Blood Glucose; D015992:Body Mass Index; D003198:Computer Simulation; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D008957:Models, Genetic
chemical_list: D001786:Blood Glucose; D007328:Insulin