Family-based association study of the restless legs syndrome loci 2 and 3 in a European population.
Three loci for the restless legs syndrome (RLS) on chromosomes 12q, 14q, and 9p (RLS1, RLS2, and RLS3) have been mapped, but no gene has been identified as yet. RLS1 has been confirmed in families from three different populations. We conducted a family-based association study of 159 European RLS trios. The subjects were genotyped using microsatellite markers evenly covering the candidate regions on chromosomes 14q and 9p with an average intermarker distance of 1.1 cM. Transmission disequilibrium tests were used to analyze the data, and empirical P values were estimated by permutation testing. On chromosome 14q, a significant association (empirical P = 0.0033) was found with a haplotype formed by markers D14S1014 and D14S1017 when analyzing all families. On chromosome 9p, no significant association in the sample of all families and only marginally significant associations were detected, with a haplotype involving markers D9S1846-D9S171 in a subset of South European trios and with a haplotype at D9S156-D9S157 in a subset of Central European trios (P = 0.0086 and 0.0077, respectively). These results represent the first confirmation of these loci in a mixed European population. Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS.
Kemlink
David
D
Institute of Human Genetics, GSF-National Research Center for Environment and Health, Munich, Germany.
Polo
Olli
O
Montagna
Pasquale
P
Provini
Federica
F
Stiasny-Kolster
Karin
K
Oertel
Wolfgang
W
de Weerd
Al
A
Nevsimalova
Sona
S
Sonka
Karel
K
Högl
Birgit
B
Frauscher
Birgit
B
Poewe
Werner
W
Trenkwalder
Claudia
C
Pramstaller
Peter P
PP
Ferini-Strambi
Luigi
L
Zucconi
Marco
M
Konofal
Eric
E
Arnulf
Isabelle
I
Hadjigeorgiou
Georgios M
GM
Happe
Svenja
S
Klein
Christine
C
Hiller
Anja
A
Lichtner
Peter
P
Meitinger
Thomas
T
Müller-Myshok
Betram
B
Winkelmann
Juliane
J
D002881:Chromosomes, Human, Pair 12 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007391:International Cooperation; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics; D012148:Restless Legs Syndrome / Q000208:ethnology* / Q000235:genetics*
D005819:Genetic Markers