دورية أكاديمية
A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis.
| العنوان: | A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis. |
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| المؤلفون: | Madireddy, L, Patsopoulos, NA, Cotsapas, C, Bos, Steffan Daniel, Beecham, Ashley, McCauley, J, Kim, K, Jia, X, Santaniello, A, Caillier, SJ, Andlauer, TFM, Barcellos, Lisa, Berge, Tone, Bernardinelli, L, Martinelli-Boneschi, F, Booth, D, Briggs, Farren, Celius, Elisabeth Gulowsen, Comabella, M, Comi, G, Cree, BAC, D'Alfonso, S, Dedham, K, Duquette, P., Dardiotis, E, Esposito, F, Gasperi, Christiane, Goris, A, Dubois, B, Gourraud, PA, Hadjigeorgiou, GM, Haines, J, Hawkins, C, Hemmer, B, Hintzen, R, Horakova, D, Isobe, N, Kalra, S, Kira, Jun-ichi, Khalil, M, Kockum, I, Lill, CM, Lincoln, Michelle, Luessi, F, Martin, R, Oturai, A, Palotie, A, Pericak-Vance, MA, Henry, R, Saarela, J, Ivinson, Adrian, Olsson, Thomas, Taylor, Bruce, Stewart, GJ, Harbo, Hanne Flinstad, Compston, A, Hauser, SL, Hafler, DA, Zipp, F, De Jager, P, Sawcer, S, Oksenberg, JR, Baranzini, SE |
| المصدر: | 2041-1723. |
| سنة النشر: | 2019 |
| المجموعة: | Universitet i Oslo: Digitale utgivelser ved UiO (DUO) |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | http://urn.nb.no/URN:NBN:no-77586Test; Madireddy, L Patsopoulos, NA Cotsapas, C Bos, Steffan Daniel Beecham, Ashley McCauley, J Kim, K Jia, X Santaniello, A Caillier, SJ Andlauer, TFM Barcellos, Lisa Berge, Tone Bernardinelli, L Martinelli-Boneschi, F Booth, D Briggs, Farren Celius, Elisabeth Gulowsen Comabella, M Comi, G Cree, BAC D'Alfonso, S Dedham, K Duquette, P. Dardiotis, E Esposito, F Gasperi, Christiane Goris, A Dubois, B Gourraud, PA Hadjigeorgiou, GM Haines, J Hawkins, C Hemmer, B Hintzen, R Horakova, D Isobe, N Kalra, S Kira, Jun-ichi Khalil, M Kockum, I Lill, CM Lincoln, Michelle Luessi, F Martin, R Oturai, A Palotie, A Pericak-Vance, MA Henry, R Saarela, J Ivinson, Adrian Olsson, Thomas Taylor, Bruce Stewart, GJ Harbo, Hanne Flinstad Compston, A Hauser, SL Hafler, DA Zipp, F De Jager, P Sawcer, S Oksenberg, JR Baranzini, SE . A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis. Nature Communications. 2019, 10; http://hdl.handle.net/10852/74486Test; 1770667; info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature Communications&rft.volume=10&rft.spage=&rft.date=2019; Nature Communications; 10; 12; https://doi.org/10.1038/s41467-019-09773-yTest; URN:NBN:no-77586; Fulltext https://www.duo.uio.no/bitstream/handle/10852/74486/1/41467_2019_Article_9773.pdfTest |
| DOI: | 10.1038/s41467-019-09773-y |
| الإتاحة: | https://doi.org/10.1038/s41467-019-09773-yTest http://hdl.handle.net/10852/74486Test http://urn.nb.no/URN:NBN:no-77586Test |
| حقوق: | Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.C6451E80 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-019-09773-y |
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