title: Suggestive evidence for linkage for restless legs syndrome on chromosome 19p13.
abstract: Five loci for restless legs syndrome (RLS) on chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1-RLS5) have been mapped in RLS families, with a recessive in the first and autosomal-dominant mode of inheritance in the latter cases. Investigations of further RLS families showed evidence for genetic locus heterogeneity. We have conducted a genome-wide linkage analysis in a large RLS family of Italian origin with 12 affected members in 3 generations using 5,861 single nucleotide polymorphisms (SNP, 6K Illumina). Linkage analysis was performed under an autosomal-dominant model with a complete penetrance, an allele frequency of 0.003 and a phenocopy rate of 0.005. The genome-wide scan resulted in suggestive evidence for linkage on chromosome 19p with maximum multipoint logarithm of the odds score of 2.61 between markers rs754292 and rs273265. The locus was replicated in a family-based association study in a set of 159 trios of European origin. This study provides evidence for a further RLS locus, thus supporting the picture of RLS as a genetically heterogenous complex trait.
authors.affiliation: Institute of Human Genetics, GSF-National Research Center for Environment and Health, Neuherberg-Munich, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Kemlink
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Plazzi
authors.forename: Roberto
authors.initials: R
authors.lastname: Vetrugno
authors.forename: Federica
authors.initials: F
authors.lastname: Provini
authors.forename: Olli
authors.initials: O
authors.lastname: Polo
authors.forename: Karin
authors.initials: K
authors.lastname: Stiasny-Kolster
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Oertel
authors.forename: Sona
authors.initials: S
authors.lastname: Nevsimalova
authors.forename: Karel
authors.initials: K
authors.lastname: Sonka
authors.forename: Birgit
authors.initials: B
authors.lastname: Högl
authors.forename: Birgit
authors.initials: B
authors.lastname: Frauscher
authors.forename: Georgios M
authors.initials: GM
authors.lastname: Hadjigeorgiou
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: Peter
authors.initials: P
authors.lastname: Lichtner
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myshok
authors.forename: Juliane
authors.initials: J
authors.lastname: Winkelmann
authors.forename: Pasquale
authors.initials: P
authors.lastname: Montagna
mesh_terms: D000328:Adult; D000368:Aged; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D004247:DNA / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007558:Italy; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012148:Restless Legs Syndrome / Q000235:genetics*
chemical_list: D004247:DNA