title: Case-control studies of gene-environment interaction: Bayesian design and analysis.
abstract: With increasing frequency, epidemiologic studies are addressing hypotheses regarding gene-environment interaction. In many well-studied candidate genes and for standard dietary and behavioral epidemiologic exposures, there is often substantial prior information available that may be used to analyze current data as well as for designing a new study. In this article, first, we propose a proper full Bayesian approach for analyzing studies of gene-environment interaction. The Bayesian approach provides a natural way to incorporate uncertainties around the assumption of gene-environment independence, often used in such an analysis. We then consider Bayesian sample size determination criteria for both estimation and hypothesis testing regarding the multiplicative gene-environment interaction parameter. We illustrate our proposed methods using data from a large ongoing case-control study of colorectal cancer investigating the interaction of N-acetyl transferase type 2 (NAT2) with smoking and red meat consumption. We use the existing data to elicit a design prior and show how to use this information in allocating cases and controls in planning a future study that investigates the same interaction parameters. The Bayesian design and analysis strategies are compared with their corresponding frequentist counterparts.
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA. bhramar@umich.edu
authors.forename: Bhramar
authors.initials: B
authors.lastname: Mukherjee
authors.forename: Jaeil
authors.initials: J
authors.lastname: Ahn
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.forename: Malay
authors.initials: M
authors.lastname: Ghosh
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
mesh_terms: D000818:Animals; D001191:Arylamine N-Acetyltransferase; D001499:Bayes Theorem; D001519:Behavior; D016022:Case-Control Studies; D002417:Cattle; D015179:Colorectal Neoplasms / Q000453:epidemiology; D004032:Diet; D004777:Environment; D004781:Environmental Exposure; D056726:Genetic Association Studies; D006801:Humans; D008460:Meat; D012307:Risk Factors; D018401:Sample Size; D012907:Smoking
chemical_list: D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human