Human disease-associated genetic variation impacts large intergenic non-coding RNA expression

PLoS Genet. 2013;9(1):e1003201. doi: 10.1371/journal.pgen.1003201. Epub 2013 Jan 17.


Recently it has become clear that only a small percentage (7%) of disease-associated single nucleotide polymorphisms (SNPs) are located in protein-coding regions, while the remaining 93% are located in gene regulatory regions or in intergenic regions. Thus, the understanding of how genetic variations control the expression of non-coding RNAs (in a tissue-dependent manner) has far-reaching implications. We tested the association of SNPs with expression levels (eQTLs) of large intergenic non-coding RNAs (lincRNAs), using genome-wide gene expression and genotype data from five different tissues. We identified 112 cis-regulated lincRNAs, of which 45% could be replicated in an independent dataset. We observed that 75% of the SNPs affecting lincRNA expression (lincRNA cis-eQTLs) were specific to lincRNA alone and did not affect the expression of neighboring protein-coding genes. We show that this specific genotype-lincRNA expression correlation is tissue-dependent and that many of these lincRNA cis-eQTL SNPs are also associated with complex traits and diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Gene Expression Regulation*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Polymorphism, Single Nucleotide / genetics*
  • Quantitative Trait Loci / genetics*
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Tissue Distribution


  • RNA, Long Noncoding

Grant support

This study was supported by grants from the Celiac Disease Consortium (an innovative cluster approved by the Netherlands Genomics Initiative and partly funded by the Dutch Government (grant BSIK03009 to CW)), the Netherlands Organization for Scientific Research (NWO-VICI grant 918.66.620 to CW, NWO-VENI grant 916.10.135 to LF), the Dutch Digestive Disease Foundation (MLDS WO11-30 to CW), and a Horizon Breakthrough grant from the Netherlands Genomics Initiative (grant 92519031 to LF). EGCUT received financing from FP7 programs (ENGAGE, OPENGENE), targeted financing from Estonian Government SF0180142s08, Estonian Research Roadmap through Estonian Ministry of Education and Research, Center of Excellence in Genomics (EXCEGEN), and University of Tartu (SP1GVARENG). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.