title: Genome-wide association study of restless legs syndrome identifies common variants in three genomic regions.
abstract: 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 protein kinase MAP2K5 and the transcription factor LBXCOR1 on chromosomes 2p, 6p and 15q, respectively. Two independent replications confirmed these association signals. Each genetic variant was associated with a more than 50% increase in risk for RLS, with the combined allelic variants conferring more than half of the risk. MEIS1 has been implicated in limb development, raising the possibility that RLS has components of a developmental disorder.
authors.affiliation: Institute of Human Genetics, GSF National Research Center of Environment and Health, D-85764 Neuherberg, Munich, Germany. janew@mpipsykl.mpg.de
authors.forename: Juliane
authors.initials: J
authors.lastname: Winkelmann
authors.forename: Barbara
authors.initials: B
authors.lastname: Schormair
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.forename: Lan
authors.initials: L
authors.lastname: Xiong
authors.forename: Shapour
authors.initials: S
authors.lastname: Jalilzadeh
authors.forename: Stephany
authors.initials: S
authors.lastname: Fulda
authors.forename: Benno
authors.initials: B
authors.lastname: Pütz
authors.forename: Gertrud
authors.initials: G
authors.lastname: Eckstein
authors.forename: Stephanie
authors.initials: S
authors.lastname: Hauk
authors.forename: Claudia
authors.initials: C
authors.lastname: Trenkwalder
authors.forename: Alexander
authors.initials: A
authors.lastname: Zimprich
authors.forename: Karin
authors.initials: K
authors.lastname: Stiasny-Kolster
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Oertel
authors.forename: Cornelius G
authors.initials: CG
authors.lastname: Bachmann
authors.forename: Walter
authors.initials: W
authors.lastname: Paulus
authors.forename: Ines
authors.initials: I
authors.lastname: Peglau
authors.forename: Ilonka
authors.initials: I
authors.lastname: Eisensehr
authors.forename: Jacques
authors.initials: J
authors.lastname: Montplaisir
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.forename: Guy
authors.initials: G
authors.lastname: Rouleau
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Florian
authors.initials: F
authors.lastname: Holsboer
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D002889:Chromosomes, Human, Pair 2; D002896:Chromosomes, Human, Pair 6; D056970:Co-Repressor Proteins; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007438:Introns; D048671:MAP Kinase Kinase 5 / Q000235:genetics; D008875:Middle Aged; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D009419:Nerve Tissue Proteins; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics; D012148:Restless Legs Syndrome / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: C522207:BTBD9 protein, human; D056970:Co-Repressor Proteins; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins; C522810:SKOR1 protein, human; D014157:Transcription Factors; D048671:MAP Kinase Kinase 5; C482563:MAP2K5 protein, human