Journal article

A genome-wide association study in progressive multiple sclerosis

F Martinelli-Boneschi, F Esposito, P Brambilla, E Lindström, G Lavorgna, J Stankovich, M Rodegher, R Capra, A Ghezzi, G Coniglio, B Colombo, M Sorosina, V Martinelli, D Booth, AB Oturai, G Stewart, HF Harbo, TJ Kilpatrick, J Hillert, JP Rubio Show all

Multiple Sclerosis Journal | SAGE PUBLICATIONS LTD | Published : 2012

Abstract

Background: The role played by genetic factors in influencing the clinical course of multiple sclerosis (MS) is not yet well established.Objective: We aimed to identify genetic variants associated with progressive MS (PrMS).Methods: We conducted a genome-wide association study (GWAS) in 197 patients with PrMS and 234 controls of Italian origin. We tested the top 20 single nucleotide polymorphisms (SNPs) with suggestive evidence of association (p-value<10-4) in two independent sets of primary progressive MS cases and controls.Results: We identified a risk-associated SNP in the HLA region in linkage disequilibrium (LD) with DRB1*1501 and DQB*0602 loci, with genome-wide significance (rs3129934T..

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University of Melbourne Researchers

Grants

Awarded by Multiple Sclerosis Foundation


Funding Acknowledgements

We are grateful to the MS patients and healthy controls for their participation in this study. We thank the ANZGENE Consortium for providing MS patients. We acknowledge the Oslo MS genetics group and especially Dr. Elisabeth Gulowsen Celius for help with collection of Norwegian patients with MS, and financial support through Norwegian Research Council. This project was partly sponsored by Merck-Serono. A patent application has been filled out entitled 'genetic markers for diagnosing primary progressive forms of multiple sclerosis' (Number: 09150721.0 - 1222) on associated SNPs. The project was also sponsored by the grant Giovani Ricercatori 2007 (D.lgs 502/92) from the Italian Ministry of Health, the Italian Foundation of Multiple Sclerosis (project: 2008/R/15) and the Institute of Experimental Neurology (INSPE). We thank the Danish Multiple Sclerosis Society and the Norwegian Research Council for financial support. Dr Martinelli Boneschi has received speaker honoraria and funding for travel from Sanofi-Aventis, Biogen-Dompe. He receives research support from the grant Giovani Ricercatori 2007 (D. lgs 502/92) from the Italian Ministry of Health, Fondazione Cariplo, and Fondazione Italiana Sclerosi Multipla. Dr Lindstrom has received travel funding from Biogen Idec and speaker honoraria from Merck Serono. Dr Stankovich is funded by grants #605511, #633275, #605526 and APP1003817 from the National Health and Medical Research Council (Australia) and grant LP110100473 from the Australian Research Council, and has received research support from Multiple Sclerosis Research Australia, the Lions Club of Townsville, the Royal Hobart Hospital Research Foundation, The Leukaemia Foundation of Australia, The David Collins Leukaemia Foundation, The Cancer Council of Tasmania, The Australian Cancer Research Foundation, Cancer Australia, The Australian Government's Department of Veterans' Affiars and Department of Foreign Relations and Trade, and Pfizer. Dr Martinelli received speaker honoraria or fundings for travels from Biogen-Dompe SG, Merck Serono, Bayer Schering Pharma, Novartis and Sanofi-Aventis Dr Oturai has served on scientific advisory boards for Novartis, has received speaker honoraria from Biogen Idec, Merck Serono, and Novartis; and has received research support from the Danish Multiple Sclerosis Society, the Warwara Larsen Foundation and the Johnsen Foundation. Dr Kilpatrick has served on scientific advisory boards for GlaxoSmithKline, Neurosciences Victoria, and the Victorian Neurotrauma Initiative; he has received funding for travel from Bayer Schering Pharma and Merck Serono; he served on the editorial board of Therapeutic Advances in Neurological Disorders; he is listed as an inventor on patents: HIV test kit method for detecting anti-HIV-I antibodies in saliva; a method of modulating cell survival and reagents useful for same; methods for the treatment and prophylaxis of demyelinating disease; and method of treatment in the field of inflammatory neurodegeneration; he receives research support from Bayer Schering Pharma, Biogen Idec, the Australian Research Council, the National Health and Medical Research Council of Australia, MS Research Australia and the National Multiple Staliclerosis Society. Dr Rubio is currently employed by GlaxoSmithKline and holds shares and options in this company. His contribution to this work was made while an employee of the Florey Neuroscience Institutes, where he was supported by the National Health and Medical Research Council (Australia) and the Australian Research Council.