Testing almost all common variants also allows us to examine general properties of genetic association signals. The NHGRI GWAS catalogue (www.genome.gov/gwastudies, accessed July 15, 2010) described 1,227 unique SNPs associated with one or more traits (p < 5×10−8). Of these, 1,185 (96.5%) are present in the low coverage CEU dataset. Under 30% of these are either annotated as nonsynonymous variants (77, 6.5%) or in substantial LD (r2 > 0.5) with a nonsynonymous variant (272, 23%). In the latter group, only 93 (8.4%) are in strong LD (r2 > 0.9) with a nonsynonymous variant. Since we tested ~95% of common variation, these results suggest that no more than a third of complex trait association signals are likely to be caused by common coding variation. Although it remains to be seen whether reported associations are better explained through weak LD to coding variants with strong effects, these results are consistent with the view that most contributions of common variation to complex traits are regulatory in nature.
