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PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome


We identified association of restless legs syndrome (RLS) with PTPRD at 9p23–24 in 2,458 affected individuals and 4,749 controls from Germany, Austria, Czechia and Canada. Two independent SNPs in the 5′ UTR of splice variants expressed predominantly in the central nervous system showed highly significant P values (rs4626664, Pnominal/λ corrected = 5.91 × 10−10, odds ratio (OR) = 1.44; rs1975197, Pnominal/λ corrected = 5.81 × 10−9, OR = 1.31). This work identifies PTPRD as the fourth genome-wide significant locus for RLS.

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Figure 1: Association results for stages 1 and 2 over the chromosomal segment analyzed.


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We are grateful to all individuals who participated in this study. We wish to thank J. Favor, B. Pütz and K. Oexle for discussions and R. Feldmann, J. Golic, K. Junghans and B. Schmick for technical assistance. We acknowledge L. Habersack, H. Rhese and J. Schmidt-Evers from the German RLS patient organization for supporting this study. Part of this work was financed by the National Genome Research Network (NGFN). The KORA study group consists of H.-E. Wichmann (speaker), R. Holle, J. John, T. Illig, C. Meisinger, A. Peters and their co-workers, who are responsible for the design and conduct of the KORA studies. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum München, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. The Canadian part of the study was supported by a Canadian Institutes of Health Research (CIHR) grant to G.R., J.M. and G.T. D.K. was supported by grant MSM0021620849, and J.V. and K.S. were supported by grant MSM0021620816. Recruitment of Czech controls was funded by grant IGA NR 8563-5, Ministry of Health of the Czech Republic.

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Authors and Affiliations



Study design: B.M.-M., T.M., J.W. Recruitment and biobanking of RLS cases: C.T., A.Z., K.S.-K., W.O., C.G.B., W. Paulus, B.H., B.F., V.G., W. Poewe, I.P., T.M., J.W. Recruitment and biobanking of KORA controls: C.G., T.I., H.-E.W. Recruitment and biobanking of Canadian RLS cases and controls: L.X., J.M., G.T., G.R. Recruitment and biobanking of Czech RLS cases and controls: D.K., P.V., J.V., K.S., S.N. Affymetrix genotyping: B.S., G.E., P.L. Sequenom genotyping: B.S., D.K., P.L. Supervision of all markers typed: P.L., J.W. Statistical analysis: D.R., S.R., B.M.-M. Clustering of Affymetrix genotypes: D.R., S.R., B.M.-M. Manuscript writing: B.S., D.K., D.R., F.H., B.M.-M., T.M., J.W.

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Correspondence to Thomas Meitinger or Juliane Winkelmann.

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Competing interests

B.S., P.L. B.M.-M., F.H., T.M. and J.W. filed a patent application (application no. 07007202.0-2401) at the European Patent Office. All other authors have no competing financial interests.

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Schormair, B., Kemlink, D., Roeske, D. et al. PTPRD (protein tyrosine phosphatase receptor type delta) is associated with restless legs syndrome. Nat Genet 40, 946–948 (2008).

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