Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1.
Juliane Winkelmann
(1, 2, 3)
,
Darina Czamara
(4)
,
Barbara Schormair
(1, 3)
,
Franziska Knauf
(1, 3)
,
Eva C. Schulte
(2)
,
Claudia Trenkwalder
(5)
,
Yves Dauvilliers
(6)
,
Olli Polo
(7, 8)
,
Birgit Högl
(9)
,
Klaus Berger
(10)
,
Andrea Fuhs
(10)
,
Nadine Gross
(2)
,
Karin Stiasny-Kolster
(11, 12)
,
Wolfgang Oertel
(12)
,
Cornelius G. Bachmann
(13)
,
Walter Paulus
(13)
,
Lan Xiong
(14)
,
Jacques Montplaisir
(15, 16)
,
Guy A. Rouleau
(14)
,
Ingo Fietze
(17)
,
Jana Vávrová
(18)
,
David Kemlink
(18)
,
Karel Sonka
(18)
,
Sona Nevsimalova
(18)
,
Siong-Chi Lin
(19)
,
Zbigniew Wszolek
(19)
,
Carles Vilariño-Güell
(19)
,
Matthew J. Farrer
(19)
,
Viola Gschliesser
(9)
,
Birgit Frauscher
(9)
,
Tina Falkenstetter
(9)
,
Werner Poewe
(9)
,
Richard P. Allen
(20)
,
Christopher J. Earley
(20)
,
William G. Ondo
(21)
,
Wei-Dong Le
(21)
,
Derek Spieler
(1, 3)
,
Maria Kaffe
(2, 3)
,
Alexander Zimprich
(22)
,
Johannes Kettunen
(23, 24)
,
Markus Perola
(23, 24)
,
Kaisa Silander
(23, 24)
,
Isabelle Cournu-Rebeix
(25)
,
Marcella Francavilla
(25)
,
Claire Fontenille
(25)
,
Bertrand Fontaine
(25)
,
Pavel Vodicka
(26)
,
Holger Prokisch
(3, 1)
,
Peter Lichtner
(1, 3)
,
Paul Peppard
(27)
,
Juliette Faraco
(28)
,
Emmanuel Mignot
(28)
,
Christian Gieger
(29)
,
Thomas Illig
(30)
,
H-Erich Wichmann
(31, 32, 33)
,
Bertram Müller-Myhsok
(4)
,
Thomas Meitinger
(1, 3)
1
Institute of Human Genetics
2 Department of Neurology
3 Institute of Human Genetics
4 Max-Planck-Institut für Psychiatrie
5 Center of Parkinsonism and Movement Disorders
6 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
7 Sleep Research Unit
8 Department of Pulmonary Medicine
9 Department of Neurology
10 Institute of Epidemiology and Social Medicine
11 Somnomar
12 Department of Neurology
13 Department of Clinical Neurophysiology
14 Center of Excellence in Neuroscience
15 Laboratoire d'étude des maladies du cerveau
16 Centre d'étude du sommeil
17 Interdisciplinary Center of Sleep Medicine
18 Department of Neurology
19 Centre for Molecular Medicine and Therapeutics
20 Department of Neurology
21 Department of Neurology
22 Department of Neurology
23 FIMM - Institute for Molecular Medicine Finland [Helsinki]
24 Department of Chronic Disease Prevention
25 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
26 Institute of Experimental Medicine
27 Department of Population Health Sciences
28 Center For Narcolepsy
29 Institute of Genetic Epidemiology
30 Unit for Molecular Epidemiology
31 Institute of Medical Informatics, Biometry, and Epidemiology
32 Institute of Epidemiology I
33 Klinikum Großhadern
2 Department of Neurology
3 Institute of Human Genetics
4 Max-Planck-Institut für Psychiatrie
5 Center of Parkinsonism and Movement Disorders
6 PSNREC - Neuropsychiatrie : recherche épidémiologique et clinique
7 Sleep Research Unit
8 Department of Pulmonary Medicine
9 Department of Neurology
10 Institute of Epidemiology and Social Medicine
11 Somnomar
12 Department of Neurology
13 Department of Clinical Neurophysiology
14 Center of Excellence in Neuroscience
15 Laboratoire d'étude des maladies du cerveau
16 Centre d'étude du sommeil
17 Interdisciplinary Center of Sleep Medicine
18 Department of Neurology
19 Centre for Molecular Medicine and Therapeutics
20 Department of Neurology
21 Department of Neurology
22 Department of Neurology
23 FIMM - Institute for Molecular Medicine Finland [Helsinki]
24 Department of Chronic Disease Prevention
25 CRICM - Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière
26 Institute of Experimental Medicine
27 Department of Population Health Sciences
28 Center For Narcolepsy
29 Institute of Genetic Epidemiology
30 Unit for Molecular Epidemiology
31 Institute of Medical Informatics, Biometry, and Epidemiology
32 Institute of Epidemiology I
33 Klinikum Großhadern
Juliane Winkelmann
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Darina Czamara
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- PersonId : 764411
- ORCID : 0000-0001-7381-904X
Yves Dauvilliers
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- PersonId : 758941
- ORCID : 0000-0003-0683-6506
David Kemlink
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- PersonId : 763638
- ORCID : 0000-0003-1398-5796
Sona Nevsimalova
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- PersonId : 763640
- ORCID : 0000-0003-0083-3742
Bertrand Fontaine
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- PersonId : 758782
- ORCID : 0000-0003-4449-8683
Emmanuel Mignot
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- IdHAL : emmanuel-mignot
- ORCID : 0000-0002-4894-2254
- IdRef : 097589977
Bertram Müller-Myhsok
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- PersonId : 763103
- ORCID : 0000-0002-0719-101X
- IdRef : 152975233
Résumé
Restless legs syndrome (RLS) is a sensorimotor disorder with an age-dependent prevalence of up to 10% in the general population above 65 years of age. Affected individuals suffer from uncomfortable sensations and an urge to move in the lower limbs that occurs mainly in resting situations during the evening or at night. Moving the legs or walking leads to an improvement of symptoms. Concomitantly, patients report sleep disturbances with consequences such as reduced daytime functioning. We conducted a genome-wide association study (GWA) for RLS in 922 cases and 1,526 controls (using 301,406 SNPs) followed by a replication of 76 candidate SNPs in 3,935 cases and 5,754 controls, all of European ancestry. Herein, we identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972, P = 9.03 × 10(-11), OR = 1.23) and a locus on 16q12.1 (rs3104767, P = 9.4 × 10(-19), OR = 1.35) in a linkage disequilibrium block of 140 kb containing the 5'-end of TOX3 and the adjacent non-coding RNA BC034767.
Domaines
Génétique
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