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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Ebers, G.C. Lancet Neurol. 7, 268–277 (2008).
Hafler, D.A. et al. N. Engl. J. Med. 357, 851–862 (2007).
Lundmark, F. et al. Nat. Genet. 39, 1108–1113 (2007).
Aulchenko, Y.S. et al. Eur. J. Hum. Genet. 12, 527–534 (2004).
Hoppenbrouwers, I.A. et al. Mult. Scler. 13, 17–24 (2007).
Zhao, C. et al. Cell 105, 587–597 (2001).
Kijima, K., Numakura, C. & Izumino, H. Hum. Genet. 116, 23–27 (2005).
Dutta, R. & Trapp, B.D. Neurology 68, S22–S31 (2007); discussion 68, S43–S54 (2007).
Dutta, R. et al. Ann. Neurol. 59, 478–489 (2006).
Craner, M.J. et al. Proc. Natl. Acad. Sci. USA 101, 8168–8173 (2004).
Waxman, S.G. Ann. Neurol. 63, 411–413 (2008).
Boldogh, I.R. & Pon, L.A. Trends Cell Biol. 17, 502–510 (2007).
Nangaku, M. et al. Cell 79, 1209–1220 (1994).
Service, S. et al. Nat. Genet. 38, 556–560 (2006).
Hoppenbrouwers, I.A. et al. Genes Immun 9, 334–337 (2008).
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.
Author information
Authors and Affiliations
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.
Corresponding author
Ethics declarations
Competing interests
Erasmus MC (R.Q. Hintzen) has filed a patent application on KIF1B in MS, number P85588PC00.
Supplementary information
Supplementary Text and Figures
Supplementary Methods (PDF 127 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ng.251
This article is cited by
-
Regulation of ciliary homeostasis by intraflagellar transport-independent kinesins
Cell Death & Disease (2024)
-
Contribution of common risk variants to multiple sclerosis in Orkney and Shetland
European Journal of Human Genetics (2021)
-
Affinity depletion versus relative protein enrichment: a side-by-side comparison of two major strategies for increasing human cerebrospinal fluid proteome coverage
Clinical Proteomics (2019)
-
Axonal transport deficits in multiple sclerosis: spiraling into the abyss
Acta Neuropathologica (2017)
-
Multiple sclerosis: getting personal with induced pluripotent stem cells
Cell Death & Disease (2015)