In the last decade, more than 1,900 genome-wide association studies (GWASs) have been published, identifying loci associated with susceptibility to over 1,000 unique traits and common diseases [4]. With the eventual goal of finding new therapies and preventative measures for common diseases, efforts are now focused on determining the functional underpinnings of these associations. Several groups have associated GWAS risk variants, mostly SNPs, with newly annotated cell-type-specific gene enhancer elements identified through epigenomic profiling studies. These enhancer variants probably play an important part in common disease susceptibility by influencing transcriptional output. Of all the genetic risk variants discovered to date, the number that impact enhancer function is estimated to far exceed the number that affect protein-coding genes or disrupt promoter function (Figure 2). Additionally, disease-associated variants in noncoding regions, particularly those that lie in cell-type-specific enhancer elements, have been estimated to explain a greater proportion of the heritability for some disorders than variants in coding regions [5]. This review focuses on the identification and interpretation of disease-associated variants that affect enhancer function. We consider the latest approaches for evaluating enhancer
