The Emerging Importance of Genetics in Epidemiologic Research II. Issues in Study Design and Gene Mapping

PURPOSE: To provide a synthesis of current approaches to the discovery of genes associated with complex human diseases by examining the joint potential of traditional epidemiologic methods and current molecular techniques for gene discovery. METHODS: A discussion of optimal approaches for defining complex disease phenotypes in genetic epidemiology, ascertainment strategies for estimating genetic influences on disease risk, genomic approaches for localizing complex-disease-susceptibility genes, and the potential synergistic effects of integrating genetic and traditional epidemiologic expertise is provided in the second part of a three-part series on the importance of genetics in epidemiologic research. RESULTS: The ability to quantify genetic influences on disease risk appears highly dependent on the measurement of specific risk factor traits, ascertainment strategies for recruiting study subjects, and a variety of genomic approaches that are rapidly facilitating our ability to identify genes influencing inherited human diseases and to quantify genetic influences on disease risk. CONCLUSIONS: Integrating population-based methods of assessing disease risk with human genetics and genome technology is critical for identifying genetic polymorphisms that influence risk of disease and for defining genetic effects on complex disease etiology.