MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis

Christina M. Lill; Brit-Maren M. Schjeide; Christiane Graetz; Maria Ban; Antonio Alcina; Miguel A. Ortiz; Jennifer Perez; Vincent Damotte; David Booth; Aitzkoa Lopez de lapuente; Linda Broer; Marcel Schilling; Denis A. Akkad; Orhan Aktas; Iraide Alloza; Alfredo Antigueedad; Rafa Arroyo; Paul Blaschke; Mathias Buttmann; Andrew Chan; Alastair Compston; Isabelle Cournu-Rebeix; Thomas Doerner; Joerg T. Epplen; Oscar Fernandez; Lisa-Ann Gerdes; Lena Guillot-Noel; Hans-Peter Hartung; Sabine Hoffjan; Guillermo Izquierdo; Anu Kemppinen; Antje Kroner; Christian Kubisch; Tania Kuempfel; Shu-Chen Li; Ulman Lindenberger; Peter Lohse; Catherine Lubetzki; Felix Luessi; Sunny Malhotra; Julia Mescheriakova; Xavier Montalban; Caroline Papeix; Lidia F. Paredes; Peter Rieckmann; Elisabeth Steinhagen-Thiessen; Alexander Winkelmann; Uwe K. Zettl; Rogier Hintzen; Koen Vandenbroeck; Graeme Stewart; Bertrand Fontaine; Manuel Comabella; Elena Urcelay; Fuencisla Matesanz; Stephen Sawcer; Lars Bertram; Frauke Zipp; Int Multiple Sclerosis Genetics; Jacob L McCauley

doi:10.1093/brain/awt101

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MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis

Journal article

Peer reviewed

MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis

Christina M. Lill, Brit-Maren M. Schjeide, Christiane Graetz, Maria Ban, Antonio Alcina, Miguel A. Ortiz, Jennifer Perez, Vincent Damotte, David Booth, Aitzkoa Lopez de lapuente, …

Brain (London, England : 1878), Vol.136(6), pp.1778-1782

2013-06-01

DOI: https://doi.org/10.1093/brain/awt101

PMCID: PMC3673463

PMID: 23739915

Abstract

Clinical Neurology

Life Sciences & Biomedicine

Neurosciences

Neurosciences & Neurology

Science & Technology

A recent genome-wide association study reported five loci for which there was strong, but sub-genome-wide significant evidence for association with multiple sclerosis risk. The aim of this study was to evaluate the role of these potential risk loci in a large and independent data set of similar to 20 000 subjects. We tested five single nucleotide polymorphisms rs228614 (MANBA), rs630923 (CXCR5), rs2744148 (SOX8), rs180515 (RPS6KB1), and rs6062314 (ZBTB46) for association with multiple sclerosis risk in a total of 8499 cases with multiple sclerosis, 8765 unrelated control subjects and 958 trios of European descent. In addition, we assessed the overall evidence for association by combining these newly generated data with the results from the original genome-wide association study by meta-analysis. All five tested single nucleotide polymorphisms showed consistent and statistically significant evidence for association with multiple sclerosis in our validation data sets (rs228614: odds ratio = 0.91, P = 2.4 x 10(-6); rs630923: odds ratio = 0.89, P = 1.2 x 10(-4); rs2744148: odds ratio = 1.14, P = 1.8 x 10(-6); rs180515: odds ratio = 1.12, P = 5.2 x 10(-7); rs6062314: odds ratio = 0.90, P = 4.3 x 10(-3)). Combining our data with results from the previous genome-wide association study by meta-analysis, the evidence for association was strengthened further, surpassing the threshold for genome-wide significance (P < 5 x 10(-8)) in each case. Our study provides compelling evidence that these five loci are genuine multiple sclerosis susceptibility loci. These results may eventually lead to a better understanding of the underlying disease pathophysiology.

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.203 Neuromuscular Disorders; 1.203.147 Multiple Sclerosis
Web Of Science research areas: Clinical Neurology; Neurosciences
ESI research areas: Neuroscience & Behavior

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Title: MANBA, CXCR5, SOX8, RPS6KB1 and ZBTB46 are genetic risk loci for multiple sclerosis
Creators: Christina M. Lill - Max Planck Society
Brit-Maren M. Schjeide - Max Planck Society
Christiane Graetz - Max
Maria Ban - Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England
Antonio Alcina - CSIC, IPBLN, Granada, Spain
Miguel A. Ortiz - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Jennifer Perez - HUVH, Ctr Esclerosi Multiple Catalunya, Cemcat, Dept Neurol Neuroimmunol, Barcelona, Spain
Vincent Damotte - Inserm
David Booth - Millennium Institute
Aitzkoa Lopez de lapuente - Univ Basque Country UPV EHU, Dept Neurosci, Neurogenomiks Lab, Leioa, Spain
Linda Broer - Univ Med Ctr, Erasmus MC, MS Ctr ErasMS, Rotterdam, Netherlands
Marcel Schilling - Max
Denis A. Akkad - Ruhr University Bochum
Orhan Aktas - Univ Dusseldorf, Dept Neurol, Fac Med, Dusseldorf, Germany
Iraide Alloza - Univ Basque Country UPV EHU, Dept Neurosci, Neurogenomiks Lab, Leioa, Spain
Alfredo Antigueedad - Hosp Basurto, Serv Neurol, Bilbao, Spain
Rafa Arroyo - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Paul Blaschke - Univ Rostock, Dept Neurol, D-18055 Rostock, Germany
Mathias Buttmann - Univ Wurzburg, Dept Neurol, Wurzburg, Germany
Andrew Chan - Ruhr University Bochum
Alastair Compston - Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England
Isabelle Cournu-Rebeix - Inserm
Thomas Doerner - Charite, Dept Med Rheumatol & Clin Immunol, D-13353 Berlin, Germany
Joerg T. Epplen - Ruhr University Bochum
Oscar Fernandez - Hosp Reg Univ Carlos Haya, Inst Neurociencias Clin, Serv Neurol, Malaga, Spain
Lisa-Ann Gerdes - Univ Munich, Inst Clin Neuroimmunol, Munich, Germany
Lena Guillot-Noel - Inserm
Hans-Peter Hartung - Univ Dusseldorf, Dept Neurol, Fac Med, Dusseldorf, Germany
Sabine Hoffjan - Ruhr University Bochum
Guillermo Izquierdo - Hosp Virgen Macarena, Unidad Esclerosis Multiple, Seville, Spain
Anu Kemppinen - Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England
Antje Kroner - Univ Wurzburg, Dept Neurol, Wurzburg, Germany
Christian Kubisch - Univ Ulm, Inst Human Genet, D-89069 Ulm, Germany
Tania Kuempfel - Univ Munich, Inst Clin Neuroimmunol, Munich, Germany
Shu-Chen Li - Max Planck Society
Ulman Lindenberger - Max Planck Society
Peter Lohse - Univ Munich, Dept Clin Chem, Munich, Germany
Catherine Lubetzki - Inserm
Felix Luessi - Focus
Sunny Malhotra - HUVH, Ctr Esclerosi Multiple Catalunya, Cemcat, Dept Neurol Neuroimmunol, Barcelona, Spain
Julia Mescheriakova - Univ Med Ctr, Erasmus MC, MS Ctr ErasMS, Rotterdam, Netherlands
Xavier Montalban - HUVH, Ctr Esclerosi Multiple Catalunya, Cemcat, Dept Neurol Neuroimmunol, Barcelona, Spain
Caroline Papeix - Inserm
Lidia F. Paredes - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Peter Rieckmann - Univ Wurzburg, Dept Neurol, Wurzburg, Germany
Elisabeth Steinhagen-Thiessen - Charite, Lipids Clin, Interdisciplinary Metab Ctr, D-13353 Berlin, Germany
Alexander Winkelmann - Univ Rostock, Dept Neurol, D-18055 Rostock, Germany
Uwe K. Zettl - Univ Rostock, Dept Neurol, D-18055 Rostock, Germany
Rogier Hintzen - Univ Med Ctr, Erasmus MC, MS Ctr ErasMS, Rotterdam, Netherlands
Koen Vandenbroeck - Univ Basque Country UPV EHU, Dept Neurosci, Neurogenomiks Lab, Leioa, Spain
Graeme Stewart - Millennium Institute
Bertrand Fontaine - Inserm
Manuel Comabella - HUVH, Ctr Esclerosi Multiple Catalunya, Cemcat, Dept Neurol Neuroimmunol, Barcelona, Spain
Elena Urcelay - Instituto de Investigación Sanitaria del Hospital Clínico San Carlos
Fuencisla Matesanz - CSIC, IPBLN, Granada, Spain
Stephen Sawcer - Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England
Lars Bertram - Max Planck Society
Frauke Zipp - Focus
Int Multiple Sclerosis Genetics
Jacob L McCauley - UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation)
Publication Details: Brain (London, England : 1878), Vol.136(6), pp.1778-1782
Publisher: Oxford Univ Press
Number of pages: 5
Grant note: Fidelity Biosciences Research Initiative Fundacion Alicia Koplowitz Walter- and Ilse-Rose-Stiftung M.FE.A.LD0002 / Max Planck Society; Foundation CELLEX PI12/00555 / FEDER-FIS 212877 / European Community's Seventh Framework Programme; European Commission PI10/1985 / Fondo de Investigaciones Sanitarias FEDER-FIS Cambridge NIHR Biomedical Research Centre; National Institute for Health Research (NIHR) RO1NS049477 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA German Research Foundation (DFG) INSERM; Institut National de la Sante et de la Recherche Medicale (Inserm); European Commission 16SV5538; 01GM1203A; NBL3; 01UW0808 / BMBF; Federal Ministry of Education & Research (BMBF) ANR-10-IAIHU-06 / program 'Investissements d'avenir'; French National Research Agency (ANR) ARSEP Cure Alzheimer's Fund AFM; Association Francaise contre les Myopathies NF-SI-0508-10335 / National Institute for Health Research; National Institute for Health Research (NIHR) R01NS049477 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) GIS-IBISA German Ministry for Education and Research (BMBF); Federal Ministry of Education & Research (BMBF) SAF2009-11491 / MINECO-FEDER
Academic Unit: Miller School of Medicine; UMMG Dept of Human Genetics (Dr. John T. Macdonald Foundation); John P. Hussman Institute for Human Genomics
Language: English
Resource Type: Journal article
PMID: 23739915
PMCID: PMC3673463
Record Identifier: 991031724246802976