A key question in the field is whether the transcripts resulting from pervasive transcription of intergenic regions are functional or the result of noisy transcription. The lincRNAs we describe are specifically regulated and contain conserved sequence, attributes inconsistent with transcriptional noise (Figure 3). Furthermore, lincRNAs were found to be strongly enriched for intergenic TASs compared to nonexpressed intergenic regions (Figure 4). This striking finding supports the possibility that many intergenic SNPs mark regions that function as lincRNAs rather than DNA elements. Because nearly half of all TASs are intergenic, it is possible that lincRNAs play a significant role in the majority of human traits and diseases thus far analyzed in GWASs. One functional lincRNA (MIAT) was first identified during the experimental interrogation of an intergenic TAS [35], and another lincRNA PTCSC3, was identified nearby a TAS found from a papillary thyroid carcinoma GWAS, perhaps representing the first of many such discoveries to come from intergenic TASs. The finding that lincRNAs are strongly enriched for TASs provides a new opportunity to revisit intergenic trait-associated regions with unknown functional mechanisms by testing whether the overlapping lincRNA is involved in the observed phenotype.
