expect same sets of susceptibility alleles to be detected by both approaches. The relatively large nominated linkage regions tagged by microsatellites may implicate common or rare variants or both within the region of interest, on the other hand, it is generally believed that only common variants can be detected by GWAS. Moreover, even if a linkage region is driven by common variants, we may still not be able to locate them in GWAS because of the stringent p values applied for defining significance in GWAS. The presence of GWAS signals outside linkage peaks might also result from the lack of power for linkage studies to detect weak genetic effects exhibited by the loci involved in complex diseases compared with association studies.119 As one can see, these unbiased approaches are powerful in marking areas in the genome; nevertheless, the areas they indicate are often large and may not be complete. In this case, hypothesis-driven studies are useful and necessary tools not only to scrutinize marked areas, but also to explore promising false-negative results and biologically plausible targets.
