title: Embracing Complex Associations in Common Traits: Critical Considerations for Precision Medicine.
abstract: Genome-wide association studies (GWAS) have identified numerous loci associated with human phenotypes. This approach, however, does not consider the richly diverse and complex environment with which humans interact throughout the life course, nor does it allow for interrelationships between genetic loci and across traits. As we move toward making precision medicine a reality, whereby we make predictions about disease risk based on genomic profiles, we need to identify improved predictive models of the relationship between genome and phenome. Methods that embrace pleiotropy (the effect of one locus on more than one trait), and gene-environment (G×E) and gene-gene (G×G) interactions, will further unveil the impact of alterations in biological pathways and identify genes that are only involved with disease in the context of the environment. This valuable information can be used to assess personal risk and choose the most appropriate medical interventions based on the genotype and environment of an individual, the whole premise of precision medicine.
authors.affiliation: Institute for Biomedical Informatics, Departments of Genetics and Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Philadelphia, PA 19104, USA.
authors.forename: Molly A
authors.initials: MA
authors.lastname: Hall
authors.affiliation: Institute for Biomedical Informatics, Departments of Genetics and Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, 3535 Market Street, Philadelphia, PA 19104, USA.
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.affiliation: Biomedical and Translational Informatics, Geisinger Health System, Danville, PA, USA; Department of Biochemistry and Molecular Biology, Center for Systems Genomics, Eberly College of Science, The Pennsylvania State University, University Park, PA, USA. Electronic address: mdritchie@geisinger.edu.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
mesh_terms: D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine