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Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci
Long non-coding RNAs are a new class of non-coding RNAs that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Nearly 90% of the phenotype-associated single-nucl...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140826/ https://www.ncbi.nlm.nih.gov/pubmed/25144376 http://dx.doi.org/10.1371/journal.pone.0105723 |
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author | Mirza, Aashiq H. Kaur, Simranjeet Brorsson, Caroline A. Pociot, Flemming |
author_facet | Mirza, Aashiq H. Kaur, Simranjeet Brorsson, Caroline A. Pociot, Flemming |
author_sort | Mirza, Aashiq H. |
collection | PubMed |
description | Long non-coding RNAs are a new class of non-coding RNAs that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Nearly 90% of the phenotype-associated single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific cis-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs. We explored sequence and structure based attributes of these lncRNAs, and also predicted the structural effects of mapped SNPs within them. We also identified lncRNAs in IBD and T1D that are under recent positive selection. Our analysis identified putative lncRNA secondary structure-disruptive SNPs within and in close proximity (+/−5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable information that could be potentially useful for future structure-function studies on lncRNAs. |
format | Online Article Text |
id | pubmed-4140826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41408262014-08-25 Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci Mirza, Aashiq H. Kaur, Simranjeet Brorsson, Caroline A. Pociot, Flemming PLoS One Research Article Long non-coding RNAs are a new class of non-coding RNAs that are at the crosshairs in many human diseases such as cancers, cardiovascular disorders, inflammatory and autoimmune disease like Inflammatory Bowel Disease (IBD) and Type 1 Diabetes (T1D). Nearly 90% of the phenotype-associated single-nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) lie outside of the protein coding regions, and map to the non-coding intervals. However, the relationship between phenotype-associated loci and the non-coding regions including the long non-coding RNAs (lncRNAs) is poorly understood. Here, we systemically identified all annotated IBD and T1D loci-associated lncRNAs, and mapped nominally significant GWAS/ImmunoChip SNPs for IBD and T1D within these lncRNAs. Additionally, we identified tissue-specific cis-eQTLs, and strong linkage disequilibrium (LD) signals associated with these SNPs. We explored sequence and structure based attributes of these lncRNAs, and also predicted the structural effects of mapped SNPs within them. We also identified lncRNAs in IBD and T1D that are under recent positive selection. Our analysis identified putative lncRNA secondary structure-disruptive SNPs within and in close proximity (+/−5 kb flanking regions) of IBD and T1D loci-associated candidate genes, suggesting that these RNA conformation-altering polymorphisms might be associated with diseased-phenotype. Disruption of lncRNA secondary structure due to presence of GWAS SNPs provides valuable information that could be potentially useful for future structure-function studies on lncRNAs. Public Library of Science 2014-08-21 /pmc/articles/PMC4140826/ /pubmed/25144376 http://dx.doi.org/10.1371/journal.pone.0105723 Text en © 2014 Mirza et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Mirza, Aashiq H. Kaur, Simranjeet Brorsson, Caroline A. Pociot, Flemming Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci |
title | Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci |
title_full | Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci |
title_fullStr | Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci |
title_full_unstemmed | Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci |
title_short | Effects of GWAS-Associated Genetic Variants on lncRNAs within IBD and T1D Candidate Loci |
title_sort | effects of gwas-associated genetic variants on lncrnas within ibd and t1d candidate loci |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140826/ https://www.ncbi.nlm.nih.gov/pubmed/25144376 http://dx.doi.org/10.1371/journal.pone.0105723 |
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