Almost half of all trait-associated SNPs (TASs) identified in genome-wide association studies are located in intergenic sequence while only a small portion are in protein coding gene exons [1]. This curious observation points to an abundance of functional elements in intergenic sequence. While some of these regions may function at the DNA level alone, it is possible that many function by encoding RNA. In fact, TASs have already been identified within or proximal to noncoding RNAs including some lincRNAs [16], [33]–[36]. We reasoned that if lincRNAs are functional, they should be enriched for TASs compared to nonexpressed intergenic regions. Indeed, we find that lincRNAs are more than 5-fold enriched for TASs compared to nonexpressed intergenic regions (Figure 4) despite an approximately equal distribution of SNPs between these regions (Figure S7). Therefore, many trait-associated intergenic regions may function by encoding lincRNAs.
