Your browser doesn't support javascript.
loading
Genome-wide significant association with seven novel multiple sclerosis risk loci.
Lill, Christina M; Luessi, Felix; Alcina, Antonio; Sokolova, Ekaterina A; Ugidos, Nerea; de la Hera, Belén; Guillot-Noël, Léna; Malhotra, Sunny; Reinthaler, Eva; Schjeide, Brit-Maren M; Mescheriakova, Julia Y; Mashychev, Andriy; Wohlers, Inken; Akkad, Denis A; Aktas, Orhan; Alloza, Iraide; Antigüedad, Alfredo; Arroyo, Rafa; Astobiza, Ianire; Blaschke, Paul; Boyko, Alexei N; Buttmann, Mathias; Chan, Andrew; Dörner, Thomas; Epplen, Joerg T; Favorova, Olga O; Fedetz, Maria; Fernández, Oscar; García-Martínez, Angel; Gerdes, Lisa-Ann; Graetz, Christiane; Hartung, Hans-Peter; Hoffjan, Sabine; Izquierdo, Guillermo; Korobko, Denis S; Kroner, Antje; Kubisch, Christian; Kümpfel, Tania; Leyva, Laura; Lohse, Peter; Malkova, Nadezhda A; Montalban, Xavier; Popova, Ekaterina V; Rieckmann, Peter; Rozhdestvenskii, Alexei S; Schmied, Christiane; Smagina, Inna V; Tsareva, Ekaterina Y; Winkelmann, Alexander; Zettl, Uwe K.
Afiliação
  • Lill CM; Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany Depart
  • Luessi F; Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
  • Alcina A; Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina López Neyra (IPBLN), CSIC, Granada, Spain.
  • Sokolova EA; Laboratory of Pharmacogenomics, Institute of Chemical Biology and Fundamental Medicine, Siberian Division, Russian Academy of Sciences, Novosibirsk, Russia Novosibirsk State University, Novosibirsk, Russia.
  • Ugidos N; Neurogenomiks Laboratory, University of the Basque Country (UPV/EHU), Leioa, Spain Achucarro Basque Center for Neuroscience, Zamudio, Spain.
  • de la Hera B; Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
  • Guillot-Noël L; Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Inserm U 1127, CNRS UMR 7225, ICM F-75013, Paris, France.
  • Malhotra S; Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya, Cemcat, Hospital Universitari Vall d´Hebron (HUVH), Barcelona, Spain.
  • Reinthaler E; Department of Neurology, Medical University of Vienna, Vienna, Austria.
  • Schjeide BM; Department of Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin, Germany.
  • Mescheriakova JY; Department of Neurology, MS Centre ErasMS, Erasmus Medical Centre, Rotterdam, The Netherlands.
  • Mashychev A; Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
  • Wohlers I; Platform for Genome Analytics, Institutes of Neurogenetics & Integrative and Experimental Genomics, University of Lübeck, Lübeck, Germany.
  • Akkad DA; Department of Human Genetics, Ruhr University, Bochum, Germany.
  • Aktas O; Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
  • Alloza I; Neurogenomiks Laboratory, University of the Basque Country (UPV/EHU), Leioa, Spain Achucarro Basque Center for Neuroscience, Zamudio, Spain IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
  • Antigüedad A; Servicio de Neurología, Hospital Universitario de Basurto, Bilbao, Spain.
  • Arroyo R; Multiple Sclerosis Unit, Neurology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
  • Astobiza I; Neurogenomiks Laboratory, University of the Basque Country (UPV/EHU), Leioa, Spain Achucarro Basque Center for Neuroscience, Zamudio, Spain.
  • Blaschke P; Department of Neurology, University of Rostock, Rostock, Germany.
  • Boyko AN; Department of Neurology and Neurosurgery, Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia.
  • Buttmann M; Department of Neurology, University of Würzburg, Würzburg, Germany.
  • Chan A; Department of Neurology, St. Josef-Hospital, Ruhr-University, Bochum, Germany.
  • Dörner T; Department of Medicine, Rheumatology, and Clinical Immunology & DRFZ, Charité University Medicine, Berlin, Germany.
  • Epplen JT; Department of Neurology, MS Centre ErasMS, Erasmus Medical Centre, Rotterdam, The Netherlands Faculty of Health, University Witten/Herdecke, Witten, Germany.
  • Favorova OO; Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia.
  • Fedetz M; Department of Cell Biology and Immunology, Instituto de Parasitología y Biomedicina López Neyra (IPBLN), CSIC, Granada, Spain.
  • Fernández O; Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain.
  • García-Martínez A; Immunology Department, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain.
  • Gerdes LA; Institute of Clinical Neuroimmunology, Campus Grosshadern, Ludwig Maximilian University, Munich, Germany.
  • Graetz C; Department of Neurology, Focus Program Translational Neuroscience, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
  • Hartung HP; Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
  • Hoffjan S; Department of Human Genetics, Ruhr University, Bochum, Germany.
  • Izquierdo G; Unidad de Esclerosis Múltiple, Hospital Universitario Virgen Macarena, Sevilla, Spain.
  • Korobko DS; Multiple Sclerosis Center, Novosibirsk Regional State Clinical Hospital, Novosibirsk, Russia.
  • Kroner A; Department of Neurology, University of Würzburg, Würzburg, Germany Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
  • Kubisch C; Institute of Human Genetics, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
  • Kümpfel T; Institute of Clinical Neuroimmunology, Campus Grosshadern, Ludwig Maximilian University, Munich, Germany.
  • Leyva L; Unidad de Gestión Clínica de Neurociencias, Instituto de Biomedicina de Málaga (IBIMA), Hospital Regional Universitario de Málaga, Málaga, Spain.
  • Lohse P; Department of Clinical Chemistry, Ludwig Maximilian University, Munich, Germany CeGaT GmbH, Tuebingen, Germany.
  • Malkova NA; Multiple Sclerosis Center, Novosibirsk Regional State Clinical Hospital, Novosibirsk, Russia Department of Clinical Neurology and Algology, Novosibirsk State Medical University, Novosibirsk, Russia.
  • Montalban X; Department of Neurology-Neuroimmunology, Centre d'Esclerosi Múltiple de Catalunya, Cemcat, Hospital Universitari Vall d´Hebron (HUVH), Barcelona, Spain.
  • Popova EV; Department of Neurology and Neurosurgery, Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia.
  • Rieckmann P; Department of Neurology, University of Würzburg, Würzburg, Germany Department of Neurology, Sozialstiftung Bamberg Hospital, Bamberg, Germany.
  • Rozhdestvenskii AS; Department of Neurology of Postgraduate Education, Omsk State Medical Academy, Omsk, Russia.
  • Schmied C; Department of Neurology, Medical University of Vienna, Vienna, Austria.
  • Smagina IV; Territorial Clinical Hospital, Barnaul, Russia Department of Nervous Diseases, Altai State Medical University, Barnaul, Russia.
  • Tsareva EY; Department of Molecular Biology and Medical Biotechnology, Pirogov Russian National Research Medical University (RNRMU), Moscow, Russia.
  • Winkelmann A; Department of Neurology, University of Rostock, Rostock, Germany.
  • Zettl UK; Department of Neurology, University of Rostock, Rostock, Germany.
J Med Genet ; 52(12): 848-55, 2015 Dec.
Article em En | MEDLINE | ID: mdl-26475045
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.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Múltipla Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Med Genet Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Esclerose Múltipla Tipo de estudo: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: J Med Genet Ano de publicação: 2015 Tipo de documento: Article