to identify its target and to test the effect of the SNP(s) on target transcript levels. Many enhancer elements are located within 100 kilobases (kb) of the genes that they regulate, but can also be located more than a megabase away, or even on separate chromosomes. Enhancers can regulate genes or long noncoding RNAs. Most genes are regulated by more than one enhancer, and many enhancers regulate more than one target gene [55,56]. The problem is further complicated by our limited knowledge of barrier elements, which block enhancer-gene interactions. The most common method of assigning an enhancer to its nearest gene is inaccurate, with false discovery rate (FDR) estimates ranging from 40% to 73% [55,57]. Refining methods for identifying the nearest gene to looking for the ‘nearest expressed gene’ still results in a high FDR, with 53% to 77% [55,58] of distal elements bypassing the nearest active transcription start site to interact with a distant gene. Clearly, proximity alone cannot be used to accurately identify the target of an enhancer SNP.
