have led to hundreds of associations of common DNA variants with over 80 diseases and traits (17) including schizophrenia, bipolar disorder, major depression, autism, attention deficit disorder, neuroticism, alcohol dependence, smoking behavior and other psychiatric or related disorders and traits (see http://www.genome.gov/gwastudies/). In addition to connecting genetic variation to disease we have learned many lessons from these studies. The newly identified variants are common and have small effect sizes, typically allelic odds ratios not exceeding 1.5 (18). The implicated genes are most often not among those considered candidates, and they are often involved in multiple disorders that were previously thought to be unrelated (18). Although the identified associations involve non-synonymous coding variants and 5 kb gene promoter regions more often than expected by chance, 88% are in the intronic or intergenic space, and only slightly more often than expected in conserved regions (17). Although it is thought, and in many cases has been shown, that many of those trait-associated variants are involved in gene regulation (19), in the majority of cases the functional link between the DNA variant and disease biology remains unclear.
