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PLoS One. 2014 Jul 15;9(7):e102612. doi: 10.1371/journal.pone.0102612. eCollection 2014.

Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes.

Author information

1
Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
2
Department of Human Genetics, McGill University, Montréal, Canada.
3
Department of Cardiovascular Science, University of Leicester, Leicester, United Kingdom; Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, United Kingdom.
4
INSERM UMRS 937, Pierre and Marie Curie University and Medical School, Paris, France.
5
William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Heart Centre, Charterhouse Square London, United Kingdom; Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
6
Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom; National Health Service Blood and Transplant, Cambridge Centre, Long Road, Cambridge, United Kingdom.

Abstract

We applied genome-wide allele-specific expression analysis of monocytes from 188 samples. Monocytes were purified from white blood cells of healthy blood donors to detect cis-acting genetic variation that regulates the expression of long non-coding RNAs. We analysed 8929 regions harboring genes for potential long non-coding RNA that were retrieved from data from the ENCODE project. Of these regions, 60% were annotated as intergenic, which implies that they do not overlap with protein-coding genes. Focusing on the intergenic regions, and using stringent analysis of the allele-specific expression data, we detected robust cis-regulatory SNPs in 258 out of 489 informative intergenic regions included in the analysis. The cis-regulatory SNPs that were significantly associated with allele-specific expression of long non-coding RNAs were enriched to enhancer regions marked for active or bivalent, poised chromatin by histone modifications. Out of the lncRNA regions regulated by cis-acting regulatory SNPs, 20% (n = 52) were co-regulated with the closest protein coding gene. We compared the identified cis-regulatory SNPs with those in the catalog of SNPs identified by genome-wide association studies of human diseases and traits. This comparison identified 32 SNPs in loci from genome-wide association studies that displayed a strong association signal with allele-specific expression of non-coding RNAs in monocytes, with p-values ranging from 6.7×10(-7) to 9.5×10(-89). The identified cis-regulatory SNPs are associated with diseases of the immune system, like multiple sclerosis and rheumatoid arthritis.

PMID:
25025429
PMCID:
PMC4099216
DOI:
10.1371/journal.pone.0102612
[Indexed for MEDLINE]
Free PMC Article

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