Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2009 May;46(5):315-8.
doi: 10.1136/jmg.2008.062992. Epub 2009 Mar 10.

Replication of restless legs syndrome loci in three European populations

D Kemlink  1 , O Polo, B Frauscher, V Gschliesser, B Högl, W Poewe, P Vodicka, J Vavrova, K Sonka, S Nevsimalova, B Schormair, P Lichtner, K Silander, L Peltonen, C Gieger, H E Wichmann, A Zimprich, D Roeske, B Müller-Myhsok, T Meitinger, J Winkelmann
Affiliations
Multicenter Study

Replication of restless legs syndrome loci in three European populations

D Kemlink et al. J Med Genet. 2009 May.

Abstract

Background: Restless legs syndrome (RLS) is associated with common variants in three intronic and intergenic regions in MEIS1, BTBD9, and MAP2K5/LBXCOR1 on chromosomes 2p, 6p and 15q.

Methods: Our study investigated these variants in 649 RLS patients and 1230 controls from the Czech Republic (290 cases and 450 controls), Austria (269 cases and 611 controls) and Finland (90 cases and 169 controls). Ten single nucleotide polymorphisms (SNPs) within the three genomic regions were selected according to the results of previous genome-wide scans. Samples were genotyped using Sequenom platforms.

Results: We replicated associations for all loci in the combined samples set (rs2300478 in MEIS1, p = 1.26 x 10(-5), odds ratio (OR) = 1.47, rs3923809 in BTBD9, p = 4.11 x 10(-5), OR = 1.58 and rs6494696 in MAP2K5/LBXCOR1, p = 0.04764, OR = 1.27). Analysing only familial cases against all controls, all three loci were significantly associated. Using sporadic cases only, we could confirm the association only with BTBD9.

Conclusion: Our study shows that variants in these three loci confer consistent disease risks in patients of European descent. Among the known loci, BTBD9 seems to be the most consistent in its effect on RLS across populations and is also most independent of familial clustering.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J. Restless Legs Syndrome Diagnosis and Epidemiology workshop at the National Institutes of Health; International Restless Legs Syndrome Study Group, Restless legs syndrome, diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med. 2003;4:101–19. - PubMed
    1. Winkelmann J, Schormair B, Lichtner P, Ripke S, Xiong L, Jalilzadeh S, Fulda S, Pütz B, Eckstein G, Hauk S, Trenkwalder C, Zimprich A, Stiasny-Kolster K, Oertel W, Bachmann CG, Paulus W, Peglau I, Eisensehr I, Montplaisir J, Turecki G, Rouleau G, Gieger C, Illig T, Wichmann HE, Holsboer F, Müller-Myhsok B, Meitinger T. Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions. Nat Genet. 2007;39:1000–6. - PubMed
    1. Stefansson H, Rye DB, Hicks A, Petursson H, Ingason A, Thorgeirsson TE, Palsson S, Sigmundsson T, Sigurdsson AP, Eiriksdottir I, Soebech E, Bliwise D, Beck JM, Rosen A, Waddy S, Trotti LM, Iranzo A, Thambisetty M, Hardarson GA, Kristjansson K, Gudmundsson LJ, Thorsteinsdottir U, Kong A, Gulcher JR, Gudbjartsson D, Stefansson K. A genetic risk factor for periodic limb movements in sleep. N Engl J Med. 2007;357:639–47. - PubMed
    1. Mercader N, Leonardo E, Azpiazu N, Serrano A, Morata G, Martinez AC, Torres M. Conserved regulation of proximodistal limb axis development by Meis1/Hth. Nature. 1999;402:425–29. - PubMed
    1. Choe SK, Sagerström CG. Paralog group 1 Hox genes regulate rhombomere 5/6 expression of vhnf1, a repressor of rostral hindbrain fates, in a Meis-dependent manner. Dev Biol. 2004;271:350–61. - PubMed

Publication types

MeSH terms