Figure 1. Rethinking disease markers. Maurano et al. have uncovered evidence from genomewide association studies that the majority of noncoding DNA regions implicated in disease may exert their effects on distant genes, not adjacent ones as previously thought.

(I) SNPs in noncoding regions were thought to affect the expression of the nearest gene (Gene A), which was imputed to be involved in disease.

(II) Maurano et al. used data from the Encyclopedia of DNA Elements (ENCODE) consortium survey of genomic interactions to study the relationship between gene expression and disease-linked SNPs. The team concluded that noncoding SNPs typically affect the expression of distant genes (Gene B), not the nearest ones. The findings shift the focus of disease gene validation away from nearby genes toward distant genes.