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Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility

Citation

Patsopoulos, NA and Baranzini, SE and Santaniello, A and Shoostari, P and Taylor, B and Charlesworth, JC and Molyneux, PD and Patrick, E and Leal, R and Griffiths, L and Broadley, SA and Vucic, S and Lechner-Scott, J and Cotsapas, C and Booth, D and Moscato, P and Stewart, G and Scott, RJ and Wong, G and Beecham, AH and James, T and Replogle, J and Vlachos, IS and McCabe, C and Pers, TH and Brandes, A and White, C and Keenan, B and Cimpean, M and Winn, P and Panteliadis, IP and Robbins, A and Andlauer, TFM and Zarzycki, O and Dubois, B and Goris, A and Sondergaard, HB and Sellebjerg, F and Sorensen, PS and Ullum, H and ThA rner, LW and Saarela, J and Cournu-Rebeix, I and Damotte, V and Fontaine, B and Guillot-Noel, L and Lathrop, M and Vukusic, S and Berthele, A and Pongratz, V and Buck, D and Gasperi, C and Graetz, C and Grummel, V and Hemmer, B and Hoshi, M and Knier, B and Korn, T and Lill, CM and Luessi, F and Muhlau, M and Zipp, F and Dardiotis, E and Agliardi, C and Amoroso, A and Barizzone, N and Benedetti, MD and Bernardinelli, L and Cavalla, P and Clarelli, F and Comi, G and Cusi, D and Esposito, F and Ferre, L and Galimberti, D and Guaschino, C and Leone, MA and Martinelli, V and Moiola, L and Salvetti, M and Sorosina, M and Vecchio, D and Zauli, A and Santoro, S and Mancini, N and ZuccalA, M and Mescheriakova, J and Van Duijn, C and Bos, SD and Celius, EG and Spurkland, A and Comabella, M and Montalban, X and Alfredsson, L and Bomfim, IL and Gomez-Cabrero, D and Hillert, J and Jagodic, M and Linden, M and Piehl, F and Jelcic, I and Martin, R and Sospedra, M and Baker, A and Ban, M and Hawkins, C and Hysi, P and Kalra, S and Karpe, F and Khadake, J and Lachance, G and Neville, M, Int Multiple Sclerosis Genetics Co, ANZgene, IIBDGC, Australia New Zealand IBDGC, Belg, Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility, Science, 365, (6460) pp. 1-13. ISSN 0036-8075 (2019) [Refereed Article]

Copyright Statement

Copyright 2019 American Association for the Advancement of Science

DOI: doi:10.1126/science.aav7188

Abstract

We analyzed genetic data of 47,429 multiple sclerosis (MS) and 68,374 control subjects and established a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 variants within the extended MHC. We used an ensemble of methods to prioritize 551 putative susceptibility genes that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we observed enrichment for MS genes in these brain-resident immune cells, suggesting that these may have a role in targeting an autoimmune process to the central nervous system, although MS is most likely initially triggered by perturbation of peripheral immune responses.

Item Details

Item Type:Refereed Article
Keywords:gene-expression, diagnostic-criteria, complex traits, risk alleles, association, autoimmune, heritability, architecture, metaanalysis, mechanisms
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurology and neuromuscular diseases
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Taylor, B (Professor Bruce Taylor)
UTAS Author:Charlesworth, JC (Dr Jac Charlesworth)
UTAS Author:Molyneux, PD (Dr Paul Molyneux)
ID Code:152908
Year Published:2019
Web of Science® Times Cited:379
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-08-26
Last Modified:2022-10-28
Downloads:0

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