Effect Size Does Matter: The Long Road to Mechanistic Insight From Genome Wide Association
The reproducible success of genome wide association studies
In the last decade, several thousand genome-wide associations (GWA) have been described and the technique has proven to be a remarkably robust approach to the identification of common alleles that contribute to disease phenotypes1. However, to date few of these highly statistically significant associations have translated into mechanistic insights2. This translational 'gap' is a consequence of several hurdles each of which is relevant to a variable extent for any specific association, but which together conspire to prevent a reproducible trajectory from genotype to phenotype. To some degree the translational gap has been partly obscured by the tendency to associate GWA signals with neighboring genes whose presumed function makes them appealing as candidates3. However, the very nature of the GWA approach and emerging data on the consequences of too rapid a jump to conclusions suggest that the 'nearest gene' or 'nearest appealing gene' strategies are unlikely to offer generalizable solutions3.
- Received October 13, 2015.
- Accepted October 14, 2015.