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 g enes associated with complex human diseases by examining the joint potentia l of traditional epidemiologic methods and current molecular techniques for gene discovery. METHODS: A discussion of optimal approaches for defining complex disease ph enotypes in genetic epidemiology, ascertainment strategies for estimating g enetic influences on disease risk, genomic approaches for localizing comple x-disease-susceptibility genes, and the potential synergistic effects of in tegrating genetic and traditional epidemiologic expertise is provided in th e second part of a three-part series on the importance of genetics in epide miologic research. RESULTS: The ability to quantify genetic influences on disease risk appears highly dependent on the measurement of specific risk factor traits, ascert ainment strategies for recruiting study subjects, and a variety of genomic approaches that are rapidly facilitating our ability to identify genes infl uencing inherited human diseases and to quantify genetic influences on dise ase risk. CONCLUSIONS: Integrating population-based methods of assessing disease risk with human genetics and genome technology is critical for identifying gene tic polymorphisms that influence risk of disease and for defining genetic e ffects on complex disease etiology. Published by Elsevier Science Inc.