Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes.
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...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0102612 |
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| author | Jonas Carlsson Almlöf Per Lundmark Anders Lundmark Bing Ge Tomi Pastinen Cardiogenics Consortium Alison H Goodall François Cambien Panos Deloukas Willem H Ouwehand Ann-Christine Syvänen |
| author_facet | Jonas Carlsson Almlöf Per Lundmark Anders Lundmark Bing Ge Tomi Pastinen Cardiogenics Consortium Alison H Goodall François Cambien Panos Deloukas Willem H Ouwehand Ann-Christine Syvänen |
| author_sort | Jonas Carlsson Almlöf |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2e9d9228294a404dafb5b8b1a3ce4588 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj-art-2e9d9228294a404dafb5b8b1a3ce45882025-08-20T02:34:07ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10261210.1371/journal.pone.0102612Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes.Jonas Carlsson AlmlöfPer LundmarkAnders LundmarkBing GeTomi PastinenCardiogenics ConsortiumAlison H GoodallFrançois CambienPanos DeloukasWillem H OuwehandAnn-Christine SyvänenWe 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.https://doi.org/10.1371/journal.pone.0102612 |
| spellingShingle | Jonas Carlsson Almlöf Per Lundmark Anders Lundmark Bing Ge Tomi Pastinen Cardiogenics Consortium Alison H Goodall François Cambien Panos Deloukas Willem H Ouwehand Ann-Christine Syvänen Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes. PLoS ONE |
| title | Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes. |
| title_full | Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes. |
| title_fullStr | Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes. |
| title_full_unstemmed | Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes. |
| title_short | Single nucleotide polymorphisms with cis-regulatory effects on long non-coding transcripts in human primary monocytes. |
| title_sort | single nucleotide polymorphisms with cis regulatory effects on long non coding transcripts in human primary monocytes |
| url | https://doi.org/10.1371/journal.pone.0102612 |
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