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Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis

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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Figure 1: Association of MS with KIF1B region in a Dutch genetically isolated population.

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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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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.

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Correspondence to Rogier Q Hintzen.

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

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Aulchenko, Y., Hoppenbrouwers, I., Ramagopalan, S. et al. Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nat Genet 40, 1402–1403 (2008). https://doi.org/10.1038/ng.251

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