title: An exposure-weighted score test for genetic associations integrating environmental risk factors.
abstract: Current methods for detecting genetic associations lack full consideration of the background effects of environmental exposures. Recently proposed methods to account for environmental exposures have focused on logistic regressions with gene-environment interactions. In this report, we developed a test for genetic association, encompassing a broad range of risk models, including linear, logistic and probit, for specifying joint effects of genetic and environmental exposures. We obtained the test statistics by maximizing over a class of score tests, each of which involves modified standard tests of genetic association through a weight function. This weight function reflects the potential heterogeneity of the genetic effects by levels of environmental exposures under a particular model. Simulation studies demonstrate the robust power of these methods for detecting genetic associations under a wide range of scenarios. Applications of these methods are further illustrated using data from genome-wide association studies of type 2 diabetes with body mass index and of lung cancer risk with smoking.
authors.affiliation: Department of Radiology, Stanford University School of Medicine, Palo Alto, California 94305, U.S.A.
authors.forename: Summer S
authors.initials: SS
authors.lastname: Han
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 9609 Medical Center Drive Suite, Rockville, Bethesda, Maryland 20852, U.S.A.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.affiliation: Public Health Foundation of India, Vasant Kunj, New Delhi 110070, India.
authors.forename: Arpita
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 9609 Medical Center Drive Suite, Rockville, Bethesda, Maryland 20852, U.S.A.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Landi
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 9609 Medical Center Drive Suite, Rockville, Bethesda, Maryland 20852, U.S.A.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, 9609 Medical Center Drive Suite, Rockville, Bethesda, Maryland 20852, U.S.A.
authors.forename: Nilanjan
authors.initials: N
authors.lastname: Chatterjee
mesh_terms: D015992:Body Mass Index; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D004781:Environmental Exposure / Q000706:statistics & numerical data*; D056726:Genetic Association Studies / Q000379:methods*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D015233:Models, Statistical; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D018511:Systems Integration
keywords: Environmental exposures; GWAS; Gene-environment interaction; SNPs; Score test