title: Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity.
abstract: BACKGROUND
  Although genome-wide association studies (GWAS) have identified hundreds of variants associated with a risk for autoimmune and immune-related disorders (AID), our understanding of the disease mechanisms is still limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). lncRNAs are known to show more cell-type specificity than protein-coding genes.
  
  
  METHODS
  We aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AIDs which have been well-defined by Immunochip analysis and by transcriptome analysis across seven populations of peripheral blood leukocytes (granulocytes, monocytes, natural killer (NK) cells, B cells, memory T cells, naive CD4(+) and naive CD8(+) T cells) and four populations of cord blood-derived T-helper cells (precursor, primary, and polarized (Th1, Th2) T-helper cells).
  
  
  RESULTS
  We show that lncRNAs mapping to loci shared between AID are significantly enriched in immune cell types compared to lncRNAs from the whole genome (α <0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five different cell types enriched (α <0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, and psoriasis; memory T and CD8(+) T cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis). Furthermore, we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved.
  
  
  CONCLUSIONS
  The observed enrichment of lncRNA transcripts in AID loci implies lncRNAs play an important role in AID etiology and suggests that lncRNA genes should be studied in more detail to interpret GWAS findings correctly. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways.
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Barbara
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authors.lastname: Hrdlickova
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Vinod
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authors.affiliation: Turku Center for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland.
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authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Daria V
authors.initials: DV
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authors.affiliation: Turku Center for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland.
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authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
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authors.affiliation: Turku Center for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland.
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authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
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authors.affiliation: Turku Center for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland.
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authors.lastname: Ullah
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Rutger
authors.initials: R
authors.lastname: Modderman
authors.affiliation: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Wayel
authors.initials: W
authors.lastname: Abdulahad
authors.affiliation: Turku Center for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland ; Department of Information and Computer Science, Aalto University, Espoo, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Lähdesmäki
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Lude
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authors.affiliation: Turku Center for Biotechnology, University of Turku, and Åbo Akademi University, Turku, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lahesmaa
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Cisca
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authors.lastname: Wijmenga
authors.affiliation: Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Sebo
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