Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs
| Autor: | Isis Ricaño-Ponce, Daria V. Zhernakova, Patrick Deelen, Oscar Luo, Xingwang Li, Aaron Isaacs, Juha Karjalainen, Jennifer Di Tommaso, Zuzanna Agnieszka Borek, Maria M. Zorro, Javier Gutierrez-Achury, Andre G. Uitterlinden, Albert Hofman, Joyce van Meurs, Mihai G. Netea, Iris H. Jonkers, Sebo Withoff, Cornelia M. van Duijn, Yang Li, Yijun Ruan, Lude Franke, Cisca Wijmenga, Vinod Kumar, Bastiaan T. Heijmans, Peter A.C. 't Hoen, Rick Jansen, Dorret I. Boomsma, René Pool, Jenny van Dongen, Jouke J. Hottenga, Marleen M.J. van Greevenbroek, Coen D.A. Stehouwer, Carla J.H. van der Kallen, Casper G. Schalkwijk, Alexandra Zhernakova, Ettje F. Tigchelaar, P. Eline Slagboom, Marian Beekman, Joris Deelen, Diana van Heemst, Jan H. Veldink, Leonard H. van den Berg, Bert A. Hofman, André G. Uitterlinden, P. Mila Jhamai, Michael Verbiest, H. Eka D. Suchiman, Marijn Verkerk, Ruud van der Breggen, Jeroen van Rooij, Nico Lakenberg, Hailiang Mei, Maarten van Iterson, Michiel van Galen, Jan Bot, Peter van 't Hof, Irene Nooren, Matthijs Moed, Martijn Vermaat, René Luijk, Marc Jan Bonder, Freerk van Dijk, Wibowo Arindrarto, Szymon M. Kielbasa, Morris A. Swertz, Erik W. van Zwet |
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| Přispěvatelé: | Biological Psychology, RS: CARIM - R1.06 - Genetic Epidemiology and Genomics of cardiovascular diseases, RS: FHML MaCSBio, Biochemie, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Molecular Neuroscience and Ageing Research (MOLAR), Stem Cell Aging Leukemia and Lymphoma (SALL), Epidemiology, Internal Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Netherlands Twin Register (NTR) Candidate gene RNA Untranslated lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] Gene Expression Genome-wide association study 030105 genetics & heredity ANNOTATION Genome Linkage Disequilibrium ACTIVATION Immunology and Allergy TRANSCRIPTION Causal genes CHROMATIN INTERACTIONS Genetics ARCHITECTURE Genome-wide association eQTLs Chromosome Mapping High-Throughput Nucleotide Sequencing CELIAC-DISEASE Genomics 3. Good health RARE VARIANTS Cytokines RNA Long Noncoding Quantitative Trait Loci Immunology RNA-sequencing Single-nucleotide polymorphism Quantitative trait locus Biology Polymorphism Single Nucleotide Article Autoimmune Diseases 03 medical and health sciences REVEALS Autophagy Humans Genetic Predisposition to Disease Gene Genome Human Genetic Variation Celiac Disease 030104 developmental biology Gene Expression Regulation Long non-coding RNAs Human genome Genome-Wide Association Study |
| Zdroj: | Journal of Autoimmunity, 68, 62-74. Academic Press Inc. Journal of Autoimmunity, 68, pp. 62-74 Journal of Autoimmunity, 68, 62-74. Elsevier Science Journal of Autoimmunity, 68, 62-74 Journal of autoimmunity Journal of Autoimmunity, 68, 62-74. ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD Journal of Autoimmunity, 68, 62-74. Academic Press Ricano-Ponce, I, Zhernakova, D V, Deelen, P, Luo, O, Li, X, Isaacs, A, Karjalainen, J, Di. Tommaso, J, Borek, Z A, Zorro, M M, Gutierrez-Achury, J, Uitterlinden, A G, Hofman, A, van Meurs, J, Boomsma, D I, Pool, R, van Dongen, J, Hottenga, J J, Neteaf, M G, Jonkers, I H, Withoff, S, van Duijn, C M, Li, Y, Ruan, Y, Franke, L, Wijmenga, C & Kumar, V 2016, ' Refined mapping of autoimmune disease associated genetic variants with gene expression suggests an important role for non-coding RNAs ', Journal of Autoimmunity, vol. 68, pp. 62-74 . https://doi.org/10.1016/j.jaut.2016.01.002 |
| ISSN: | 0896-8411 |
| Popis: | Contains fulltext : 171367.pdf (Publisher’s version ) (Open Access) Genome-wide association and fine-mapping studies in 14 autoimmune diseases (AID) have implicated more than 250 loci in one or more of these diseases. As more than 90% of AID-associated SNPs are intergenic or intronic, pinpointing the causal genes is challenging. We performed a systematic analysis to link 460 SNPs that are associated with 14 AID to causal genes using transcriptomic data from 629 blood samples. We were able to link 71 (39%) of the AID-SNPs to two or more nearby genes, providing evidence that for part of the AID loci multiple causal genes exist. While 54 of the AID loci are shared by one or more AID, 17% of them do not share candidate causal genes. In addition to finding novel genes such as ULK3, we also implicate novel disease mechanisms and pathways like autophagy in celiac disease pathogenesis. Furthermore, 42 of the AID SNPs specifically affected the expression of 53 non-coding RNA genes. To further understand how the non-coding genome contributes to AID, the SNPs were linked to functional regulatory elements, which suggest a model where AID genes are regulated by network of chromatin looping/non-coding RNAs interactions. The looping model also explains how a causal candidate gene is not necessarily the gene closest to the AID SNP, which was the case in nearly 50% of cases. |
| Databáze: | OpenAIRE |
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