Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions

@article{Winkelmann2007GenomewideAS,
  title={Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions},
  author={Juliane Winkelmann and Barbara Schormair and Peter Lichtner and Stephan Ripke and Lan Xiong and Shapour Jalilzadeh and Stephany Fulda and Benno P{\"u}tz and Gertrud Eckstein and Stephanie Hauk and Claudia Trenkwalder and Alexander Zimprich and Karin Stiasny‐Kolster and Wolfgang Hermann Oertel and Cornelius G. Bachmann and Walter Paulus and Ines Peglau and Ilonka Eisensehr and Jacques Y. Montplaisir and Gustavo Turecki and Guy A. Rouleau and Christian Gieger and Thomas Illig and Heinz-Erich Wichmann and Florian Holsboer and Bertram M{\"u}ller-Myhsok and Thomas Meitinger},
  journal={Nature Genetics},
  year={2007},
  volume={39},
  pages={1000-1006}
}
Restless legs syndrome (RLS) is a frequent neurological disorder characterized by an imperative urge to move the legs during night, unpleasant sensation in the lower limbs, disturbed sleep and increased cardiovascular morbidity. In a genome-wide association study we found highly significant associations between RLS and intronic variants in the homeobox gene MEIS1, the BTBD9 gene encoding a BTB(POZ) domain as well as variants in a third locus containing the genes encoding mitogen-activated… 
Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1
TLDR
Six RLS susceptibility loci of genome-wide significance are identified, two of them novel: an intergenic region on chromosome 2p14 (rs6747972), and a locus on 16q12.1 (rs3104767), a linkage disequilibrium block of 140 kb containing the 5′-end of TOX3 and the adjacent non-coding RNA BC034767.
Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2 p 14 and 16 q 12 . 1
TLDR
A genome-wide association study for RLS is conducted followed by a replication of 76 candidate SNPs in 3,935 cases and 5,754 controls, all of European ancestry, and six RLS susceptibility loci are identified, two of them novel: an intergenic region on chromosome 2p14 and 16q12.1.
Variant screening of the coding regions of MEIS1 in patients with restless legs syndrome
TLDR
The coding regions and exon-intron boundaries of MEIS1 are screened for variants, which by exerting a strong phenotypic effect could provide a basis for assessing the function of the gene in RLS.
Genetics of restless legs syndrome
TLDR
Genome-wide association studies identified variants within intronic or intergenic regions of MEIS1, BTBD9, and MAP2K5/LBOXCOR1 andMEIS1 and LBXCOR1 that have weak and moderate effects and increase the risk of developing RLS.
A novel locus for restless legs syndrome maps to chromosome 19p in an Irish pedigree
TLDR
A genome-wide linkage analysis in an Irish autosomal dominant RLS pedigree with 11 affected members provides evidence of a novel RLS locus and provides further evidence that RLS is a genetically heterogenous disorder.
MEIS1 intronic risk haplotype associated with restless legs syndrome affects its mRNA and protein expression levels.
TLDR
Data suggest that reduced expression of the MEIS1 gene, possibly through intronic cis-regulatory element(s), predisposes to RLS.
A Novel Locus for Restless Legs Syndrome on Chromosome 13q
TLDR
A genetic linkage at chromosome 13 in a RLS family is demonstrated and this result shows strong genetic linkage to this locus, which supports the genetic heterogeneity in the pathogenesis of this syndrome.
MEIS1 and Restless Legs Syndrome: A Comprehensive Review
TLDR
The links to iron and the enhancer activity of the HCNRs of MEIS1 suggest promising links to RLS pathways, however more in-depth studies on this gene's function are required.
Association of restless legs syndrome variants in Korean patients with restless legs syndrome.
TLDR
The results suggest that the role of BTBD9 in the pathogenesis of restless legs syndrome is more universal across populations than previously reported and more efforts should be focused on the roleof epistasis in the genetic architecture of restless Legs syndrome.
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