A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis
| Autor: | Seema Kalra, Graeme J. Stewart, Katrina Dedham, Tfm Andlauer, Frauke Zipp, X Jia, Adam Santaniello, Bertrand Fontaine, Stacy J Caillier, Giancarlo Comi, Hanne F. Harbo, Ashley Beecham, Lisa F. Barcellos, Jacob L. McCauley, Aarno Palotie, P. L. De Jager, Ji Kira, Noriko Isobe, B. Hemmer, Lincoln, Farren B.S. Briggs, Christina M. Lill, Sergio E. Baranzini, Booth, F. Martinelli-Boneschi, A. Oturai, Pierre Duquette, Janna Saarela, A Compston, Roland G. Henry, D Efthimios, Chris Cotsapas, Jonathan L. Haines, Clive Hawkins, Federica Esposito, David A. Hafler, Giorgos M. Hadjigeorgiou, Elisabeth Gulowsen Celius, Stephen Sawcer, Lohith Madireddy, Oksenberg, Christiane Gasperi, Bac Cree, Luisa Bernardinelli, Felix Luessi, A Ivinson, Nikolaos A. Patsopoulos, Steffan D. Bos, Tomas Olsson, Bénédicte Dubois, Ingrid Kockum, Dana Horakova, Margaret A. Pericak-Vance, R Q Hintzen, An Goris, Sandra D'Alfonso, Tone Berge, Michael Khalil, Stephen L. Hauser, Bruce V. Taylor, Kicheol Kim, Roland Martin, Pierre-Antoine Gourraud, Manuel Comabella |
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| Přispěvatelé: | Apollo - University of Cambridge Repository, Immunology, Neurology, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Institute for Molecular Medicine Finland, Janna Saarela / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
General Physics and Astronomy Genome-wide association study 02 engineering and technology Neurodegenerative Genome informatics Genome-wide association studies PATHWAY Genes Regulator 2.1 Biological and endogenous factors GWAS Aetiology lcsh:Science CYTOSCAPE Multidisciplinary Systems Biology 1184 Genetics developmental biology physiology Single Nucleotide RC346 021001 nanoscience & nanotechnology ddc Multidisciplinary Sciences Trait Science & Technology - Other Topics 0210 nano-technology Biotechnology EXPRESSION Cell type Cellular signalling networks Multiple Sclerosis Genotype POLYGENIC RISK SCORE Science Systems biology Computational biology Biology Autoimmune Disease Polymorphism Single Nucleotide Article General Biochemistry Genetics and Molecular Biology Multiple sclerosis 03 medical and health sciences Immune system Clinical Research MD Multidisciplinary Genetics medicine Humans Genetic Predisposition to Disease Polymorphism GENOME-WIDE ASSOCIATION Author Correction Gene Genetic association Science & Technology Inflammatory and immune system Regulator Human Genome Neurosciences General Chemistry medicine.disease Brain Disorders International Multiple Sclerosis Genetics Consortium 030104 developmental biology Genes Gene Expression Regulation lcsh:Q 3111 Biomedicine Genome-Wide Association Study |
| Zdroj: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-12 (2019) International Multiple Sclerosis Genetics Consortium,. (2019). A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.. Nature communications, 10(1), 2236. doi: 10.1038/s41467-019-09773-y. UCSF: Retrieved from: http://www.escholarship.org/uc/item/5f91v8cb Nature communications, vol 10, iss 1 Nature Communications, 10:2236. Nature Publishing Group Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona International Multiple Sclerosis Genetics Consortium 2019, ' A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis ', Nature Communications, vol. 10, no. 1, 2236 . https://doi.org/10.1038/s41467-019-09773-y |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-09773-y. |
| Popis: | Genome-wide association studies (GWAS) have identified more than 50,000 unique associations with common human traits. While this represents a substantial step forward, establishing the biology underlying these associations has proven extremely difficult. Even determining which cell types and which particular gene(s) are relevant continues to be a challenge. Here, we conduct a cell-specific pathway analysis of the latest GWAS in multiple sclerosis (MS), which had analyzed a total of 47,351 cases and 68,284 healthy controls and found more than 200 non-MHC genome-wide associations. Our analysis identifies pan immune cell as well as cell-specific susceptibility genes in T cells, B cells and monocytes. Finally, genotype-level data from 2,370 patients and 412 controls is used to compute intra-individual and cell-specific susceptibility pathways that offer a biological interpretation of the individual genetic risk to MS. This approach could be adopted in any other complex trait for which genome-wide data is available. Genome-wide association studies (GWAS) have so far uncovered more than 200 loci for multiple sclerosis (MS). Here, the authors integrate data from various sources for a cell type-specific pathway analysis of MS GWAS results that specifically highlights the involvement of the immune system in disease pathogenesis. |
| Databáze: | OpenAIRE |
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