Abstract

The few loci associated with multiple sclerosis (MS) are all related to immune function. We report a GWA study identifying a new locus replicated in 2,679 cases and 3,125 controls. An rs10492972[C] variant located in the KIF1B gene was associated with MS with an odds ratio of 1.35 (P = 2.5 × 10−10). KIF1B is a neuronally expressed gene plausibly implicated in the irreversible axonal loss characterizing MS in the long term.

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Acknowledgements

This study was supported by grants from MS Research Netherlands (R.Q.H. and C.M.v.D.), the Erasmus University Trust Fund, The Netherlands Organisation for Scientific Research (ZON-MW, R.Q.H.), the Erasmus MC and the Multiple Sclerosis Society of Canada Scientific Research Foundation and the Multiple Sclerosis Society of the United Kingdom (S.V.R., G.C.E.). The GRIP study is supported by Centre for Medical Systems Biology (CMSB). The Stockholm part of the study was supported by the Bibbi and Nils Jensen Foundation, by the Swedish Research Council and by the EU project no. LSHM-CT-2005-018637, NeuroproMiSe. We are grateful to all participants and their relatives; general practitioners and neurologists for their contributions; P. Veraart for her help in genealogy; D. Lont and the personnel of the VIB Genetic Service Facility for genotyping; and P. Snijders for his help in data collection.

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Author notes

    • Yurii S Aulchenko
    •  & Ilse A Hoppenbrouwers

    These authors contributed equally to this work.

Affiliations

  1. Genetic Epidemiology Unit, Department of Epidemiology and Biostatistics and Clinical Genetics, Erasmus MC, Rotterdam, 3000 CA, The Netherlands.

    • Yurii S Aulchenko
    • , Linda Broer
    • , Ben A Oostra
    •  & Cornelia M van Duijn
  2. Department of Neurology, MS Centre ErasMS, Erasmus MC, Rotterdam, 3000 CA, The Netherlands.

    • Ilse A Hoppenbrouwers
    • , Linda Broer
    • , Naghmeh Jafari
    •  & Rogier Q Hintzen
  3. Wellcome Trust Centre for Human Genetics and Department of Clinical Neurology, University of Oxford, Oxford, OX3 9DU, UK.

    • Sreeram V Ramagopalan
    •  & George C Ebers
  4. Department of Neurology, Karolinska Institute, Stockholm, SE-141 86, Sweden.

    • Jan Hillert
    • , Jenny Link
    • , Wangko Lundström
    •  & Eva Greiner
  5. Department of Medical Genetics, Division of Neurology, University of British Columbia, Vancouver V6T 2B5, Canada.

    • A Dessa Sadovnick
  6. Applied Molecular Genomics and Neurodegenerative Brain Diseases Groups, Department of Molecular Genetics, Flanders Institute of Biotechnology (VIB), 2610 Antwerpen, Belgium.

    • Dirk Goossens
    • , Christine Van Broeckhoven
    •  & Jurgen Del-Favero
  7. University of Antwerp, 2610 Antwerpen, Belgium.

    • Dirk Goossens
    • , Christine Van Broeckhoven
    •  & Jurgen Del-Favero

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Contributions

R.Q.H., C.M.v.D., G.C.E. and J.H. designed the study; I.A.H., N.J., J.H., A.D.S., G.C.E. and R.Q.H. performed collection of data; Y.S.A., I.A.H., S.V.R. and L.B. performed statistical analysis; J.D.-F., D.G., B.A.O., S.V.R., J.L., W.L., E.G. and C.V.B. coordinated the genotyping; Y.S.A., R.Q.H., C.M.v.D., I.A.H., S.V.R., G.C.E., J.H., J.D.-F. and B.A.O. wrote the manuscript.

Competing interests

Erasmus MC (R.Q. Hintzen) has filed a patent application on KIF1B in MS, number P85588PC00.

Corresponding author

Correspondence to Rogier Q Hintzen.

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DOI

https://doi.org/10.1038/ng.251

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