In genetic association studies of complex diseases, case-parent-trio designs involve the collection of data from affected offspring and their parents. This design is well-suited to diseases of early onset, such as type 1 diabetes and childhood leukemia. Unlike the case-control design, the case-parent design is robust to bias from ethnic differences between cases and controls and it enables investigation of parent-of-origin effects for genetic risk factors. While the use of the case-parent design for finding genetic associations has been well studied, its use for uncovering gene-environment interactions is less well-understood. We review two existing ad-hoc approaches to explore gene-environment interaction from case-parent trios and illustrate their potential bias. We propose an alternate penalized likelihood approach that does not suffer from such bias and illustrate its use on simulated data. We conclude with some directions for future research. This is joint work with Ji-Hyung Shin and Brad McNeney.
Group for Research in Decision Analysis