Year: 2015
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. METHODS: The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. RESULTS: Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5×10(-8)) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03×10(-12)), CD28 (rs6435203, p=1.35×10(-9)), LPP (rs4686953, p=3.35×10(-8)), ETS1 (rs3809006, p=7.74×10(-9)), DLEU1 (rs806349, p=8.14×10(-12)), LPIN3 (rs6072343, p=7.16×10(-12)) and IFNGR2 (rs9808753, p=4.40×10(-10)). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. CONCLUSIONS: This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases.
Source: Journal of Medical Genetics
Authors: Christina M Lill, Felix Luessi, Antonio Alcina, Ekaterina A Sokolova, Nerea Ugidos, Belén de la Hera, Léna Guillot-Noël, Sunny Malhotra, Eva Reinthaler, Brit-Maren M Schjeide, Julia Y Mescheriakova, Andriy Mashychev, Inken Wohlers, Denis A Akkad, Orhan Aktas, Iraide Alloza, Alfredo Antigüedad, Rafa Arroyo, Ianire Astobiza, Paul Blaschke, Alexei N Boyko, Mathias Buttmann, Andrew Chan, Thomas Dörner, Joerg T Epplen, Olga O Favorova, Maria Fedetz, Oscar Fernández, Angel García-Martínez, Lisa-Ann Gerdes, Christiane Graetz, Hans-Peter Hartung, Sabine Hoffjan, Guillermo Izquierdo, Denis S Korobko, Antje Kroner, Christian Kubisch, Tania Kümpfel, Laura Leyva, Peter Lohse, Nadezhda A Malkova, Xavier Montalban, Ekaterina V Popova, Peter Rieckmann, Alexei S Rozhdestvenskii, Christiane Schmied, Inna V Smagina, Ekaterina Y Tsareva, Alexander Winkelmann, Uwe K Zettl, Harald Binder, Isabelle Cournu-Rebeix, Rogier Hintzen, Alexander Zimprich, Manuel Comabella, Bertrand Fontaine, Elena Urcelay, Koen Vandenbroeck, Maxim Filipenko, Fuencisla Matesanz, Frauke Zipp, Lars Bertram
Institutions: University Medical Center of the Johannes Gutenberg University Mainz, Max Planck Institute for Molecular Genetics, University of Lübeck, Consejo Superior de Investigaciones Científicas, Instituto de Parasitología y Biomedicina "López - Neyra", Russian Academy of Sciences, Novosibirsk State University, Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, University of the Basque Country, Achucarro Basque Center for Neuroscience, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos, Centre National de la Recherche Scientifique, Inserm, Institut du Cerveau, Vall d'Hebron Hospital Universitari, Centre d'Esclerosi Múltiple de Catalunya, Medical University of Vienna, Erasmus MC, Ruhr University Bochum, Heinrich Heine University Düsseldorf, Ikerbasque, Hospital de Basurto, University of Rostock, Pirogov Russian National Research Medical University, University of Würzburg, St. Josef-Hospital, German Rheumatism Research Centre, Charité – Universitätsmedizin Berlin, Witten/Herdecke University, Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga, Institut für Klinische Neuroimmunologie, Ludwig-Maximilians-Universität München, Hospital Universitario Virgen Macarena, Medical College of Wisconsin, University Medical Center Hamburg-Eppendorf, CeGaT (Germany), Novosibirsk State Medical University, Sozialstiftung Bamberg, Omsk State Medical University, Altai State Medical University, Regional State Budget Health Care Institution "Regional Clinical Hospital", Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Imperial College London
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques, Fundación Alicia Koplowitz, Agence Nationale de la Recherche, Institut National de la Santé et de la Recherche Médicale, Russian Foundation for Basic Research, Eusko Jaurlaritza, Johannes Gutenberg-Universität Mainz, Russian Science Foundation, Red Española de Esclerosis Múltiple, Junta de Andalucía, Instituto de Salud Carlos III, European Regional Development Fund
Awards: G1258743643, G2017455146, G2436573716, G3103753459, Identificación de variantes causales reguladoras en esclerosis múltiple y actividad patogénica asociada, G5505043327, G6507690662, G7240651115, Variantes genéticas asociadas a neurodegeneración en esclerosis múltiple obtenidas mediante GWAS, G8600537192
OpenAlex ID: W2183545298