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A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis


Madireddy, L and Patsopoulos, NA and Cotsapas, C and Bos, SD and Beecham, A and McCauley, J and Kim, K and Jia, X and Santaniello, A and Caillier, SJ and Andlauer, TFM and Barcellos, LF and Berge, T and Bernardinelli, L and Martinelli-Boneschi, F and Booth, DR and Briggs, F and Celius, EG and Comabella, M and Comi, G and Cree, BAC and D'Alfonso, S and Dedham, K and Duquette, P and Efthimios, D and Esposito, F and Fontaine, B and Gasperi, C and Goris, A and Dubois, B and Gourraud, PA and Hadjigeorgiou, G and Haines, J and Hawkins, C and Hemmer, B and Hintzen, R and Horakova, D and Isobe, N and Kalra, S and Kira, Ji and Khalil, M and Kockum, I and Lill, CM and Lincoln, MR and Luessi, F and Martin, R and Oturai, A and Palotie, A and Pericak-Vance, MA and Henry, R and Saarela, J and Ivinson, A and Olsson, T and Taylor, BV and Stewart, GJ and Harbo, HF and Compston, A and Hauser, SL and Hafler, DA and Zipp, F and De Jager, P and Sawcer, S and Oksenberg, JR and Baranzini, SE, A systems biology approach uncovers cell-specific gene regulatory effects of genetic associations in multiple sclerosis, Nature Communications, 10 Article 2236. ISSN 2041-1723 (2019) [Refereed Article]


Copyright Statement

Copyright 2019 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1038/s41467-019-09773-y


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.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Central nervous system
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Taylor, BV (Professor Bruce Taylor)
ID Code:133624
Year Published:2019
Web of Science® Times Cited:46
Deposited By:Menzies Institute for Medical Research
Deposited On:2019-07-04
Last Modified:2022-08-23
Downloads:29 View Download Statistics

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