In the recent past, other venues of research (genome-wide linkage scans and microarray expression profiling experiments)30,31 had been celebrated as “hypothesis-free” and unbiased approaches, considered to be liberated from the need of restrictive presumptions about the causative molecular mechanisms of disease. Nevertheless, these techniques fell short from providing a comprehensive picture of complex disorders genetics. It is important to acknowledge the underlying assumptions of GWAS, since in fact all biological research is based on some hypotheses, although they may not be always explicitly stated.32 More hypotheses of these experiments regarding what is actually interrogated in genome-wide screens may also reveal themselves as the understanding of the molecular mechanisms progresses. Unless the inherent limitations of GWAS are addressed, and complementary genetic analysis methods, such as targeted or whole-genome sequencing, are implemented, the full advantage of genomic scans of human variation will not be realized.
