Linkage disequilibrium screening for multiple sclerosis implicates JAG1 and POU2AF1 as susceptibility genes in Europeans.

Maria Ban, David Booth, Robert Heard, Graeme Stewart, An Goris, Koen Vandenbroeck, Bénédicte Dubois, Mikko Laaksonen, Jorma Ilonen, Mehdi Alizadeh, Gilles Edan, Marie Claude Babron, David Brassat, Michael Clanet, Isabelle Cournu-Rebeix, Bertrand Fontaine, Gilbert Semana, Rene Goedde, Jorg Epplen, Alexandra Weber, Carmen Infante-Duarte, Frauke Zipp, Cecilia Rajda, Krisztina Bencsik, László Vécsei, Shirley Heggarty, Colin Graham, Stanley Hawkins, Maria Liguori, Patricia Momigliano-Richiardi, Domenico Caputo, Luigi M E Grimaldi, Maurizio Leone, Luca Massacesi, Clara Milanese, Marco Salvetti, Giovani Savettieri, Maria Trojano, Bartosz Bielecki, Marcin P Mycko, Krzysztof Selmaj, Monica Santos, Patricia Maciel, Clara Pereira, Ana Silva, Berta Martins Silva, Francesca Coraddu, Maria Giovanna Marrosu, Eva Akesson, Jan Hillert, Pameli Datta, Annette Oturai, Hanne F Harbo, Anne Spurkland, Robert Goertsches, Pablo Villoslada, Mefkure Eraksoy, Anke Hensiek, Alastair Compston, Efrosini Setakis, Julia Gray, Tai Wai Yeo, Stephen Sawcer

Journal: Journal of neuroimmunology 2006;179(1-2):108-16

PMID: 16934875

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Abstract

By combining all the data available from the Genetic Analysis of Multiple sclerosis in EuropeanS (GAMES) project, we have been able to identify 17 microsatellite markers showing consistent evidence for apparent association. As might be expected five of these markers map within the Major Histocompatibility Complex (MHC) and are in LD with HLA-DRB1. Individual genotyping of the 12 non-MHC markers confirmed association for three of them--D11S1986, D19S552 and D20S894. Association mapping across the candidate genes implicated by these markers in 937 UK trio families revealed modestly associated haplotypes in JAG1 (p=0.019) on chromosome 20p12.2 and POU2AF1 (p=0.003) on chromosome 11q23.1.

Address: University of Cambridge, Department of Clinical Neurosciences, Addenbrooke's Hospital, Hills Road, Cambridge, UK. [email protected]

DOI: 10.1016/j.jneuroim.2006.06.003