Genome-wide association (GWA) studies have revolutionized the search for common genetic variants that influence individual risk for complex diseases. Before this revolution, the discovery of genetic associations was dominated by candidate gene studies that used targeted gene approaches. Examination of these previous gene association studies demonstrates that most reported associations are not consistently replicated (Hirschhorn et al., 2002) and the strength of genetic associations in initial studies commonly erodes in subsequent research (Ioannidis et al., 2001). Despite this suggested irreproducibility, many candidate gene association studies continue to be published annually (Yu et al., 2008).
