Genetic and environmental factors are critical elements in most common complex disease. Genetics is increasingly being recognized to play a substantive role in the susceptibility, prognosis, and treatment of common diseases. Due to recent and rapid advancements in characterization of genetic variants and large-scale genotyping platforms, multiple genes and genetic variants have now been identified for common, complex diseases. The most efficient method for gene identification at present appears to be large-scale association-based studies, which integrate genetic and epidemiological principles. As the strategy for gene identification studies has shifted toward genetic association-based methods rather than traditional linkage analysis, epidemiological methods are increasingly being integrated into genetic investigations and in public health research. Consequently, the disciplines of genetics and epidemiology, which historically have functioned separately, have been integrated into a hybrid discipline referred to as genetic epidemiology. In this chapter, we review methods for establishing the genetic burden of complex genetic disease, followed by methods for gene and/or genetic variant identification. When appropriate, we will highlight the epidemiological issues and clinical applications that guide these methods.
Keywords: Association studies; Genetic epidemiology; Genotyping; Heritability studies; Linkage disequilibrium; Linkage studies; Next-generation sequencing; Whole-genome-wide association scans.