Journal
PLOS GENETICS
Volume 9, Issue 1, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1003201
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Funding
- Celiac Disease Consortium
- Dutch Government [BSIK03009]
- Netherlands Organization for Scientific Research [918.66.620, 916.10.135]
- Dutch Digestive Disease Foundation [MLDS WO11-30]
- Horizon Breakthrough grant from the Netherlands Genomics Initiative [92519031]
- FP7 program ENGAGE
- FP7 program OPENGENE
- Estonian Government [SF0180142s08]
- Estonian Research Roadmap through Estonian Ministry of Education and Research
- Center of Excellence in Genomics (EXCEGEN)
- University of Tartu (SP1GVARENG)
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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.
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