Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry : a meta-analysis

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Schormair , B , Zhao , C , Bell , S , Tilch , E , Salminen , A V , Puetz , B , Dauvilliers , Y , Stefani , A , Hoegl , B , Poewe , W , Kemlink , D , Sonka , K , Bachmann , C G , Paulus , W , Trenkwalder , C , Oertel , W H , Hornyak , M , Teder-Laving , M , Metspalu , A , Hadjigeorgiou , G M , Polo , O , Fietze , I , Ross , O A , Wszolek , Z , Butterworth , A S , Soranzo , N , Ouwehand , W H , Roberts , D J , Danesh , J , Allen , R P , Earley , C J , Ondo , W G , Xiong , L , Montplaisir , J , Gan-Or , Z , Perola , M , Vodicka , P , Dina , C , Franke , A , Tittmann , L , Stewart , A F R , Shah , S H , Gieger , C , Peters , A , Rouleau , G A , Berger , K , Oexle , K , Di Angelantonio , E , Hinds , D A , Mueller-Myhsok , B , Collaboration 23andMe Res Team & DESIR Study Grp 2017 , ' Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry : a meta-analysis ' , Lancet Neurology , vol. 16 , no. 11 , pp. 898-907 . https://doi.org/10.1016/S1474-4422(17)30327-7

Title: Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry : a meta-analysis
Author: Schormair, Barbara; Zhao, Chen; Bell, Steven; Tilch, Erik; Salminen, Aaro V.; Puetz, Benno; Dauvilliers, Yves; Stefani, Ambra; Hoegl, Birgit; Poewe, Werner; Kemlink, David; Sonka, Karel; Bachmann, Cornelius G.; Paulus, Walter; Trenkwalder, Claudia; Oertel, Wolfgang H.; Hornyak, Magdolna; Teder-Laving, Maris; Metspalu, Andres; Hadjigeorgiou, Georgios M.; Polo, Olli; Fietze, Ingo; Ross, Owen A.; Wszolek, Zbigniew; Butterworth, Adam S.; Soranzo, Nicole; Ouwehand, Willem H.; Roberts, David J.; Danesh, John; Allen, Richard P.; Earley, Christopher J.; Ondo, William G.; Xiong, Lan; Montplaisir, Jacques; Gan-Or, Ziv; Perola, Markus; Vodicka, Pavel; Dina, Christian; Franke, Andre; Tittmann, Lukas; Stewart, Alexandre F. R.; Shah, Svati H.; Gieger, Christian; Peters, Annette; Rouleau, Guy A.; Berger, Klaus; Oexle, Konrad; Di Angelantonio, Emanuele; Hinds, David A.; Mueller-Myhsok, Bertram; Collaboration 23andMe Res Team; DESIR Study Grp
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2017-11
Language: eng
Number of pages: 10
Belongs to series: Lancet Neurology
ISSN: 1474-4422
URI: http://hdl.handle.net/10138/228242
Abstract: Background Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. Methods In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15126 cases and 95 725 controls of European ancestry. We identified common variants by fixed-effect inverse-variance meta-analysis. Significant genome-wide signals (p Findings We identified and replicated 13 new risk loci for restless legs syndrome and confirmed the previously identified six risk loci. MEIS1 was confirmed as the strongest genetic risk factor for restless legs syndrome (odds ratio 1.92, 95% CI 1 85-1.99). Gene prioritisation, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance (associated with SEMA6D), synapse formation (NTNG1), and neuronal specification (HOXB cluster family and MYT1). Interpretation Identification of new candidate genes and associated pathways will inform future functional research. Advances in understanding of the molecular mechanisms that underlie restless legs syndrome could lead to new treatment options. We focused on common variants; thus, additional studies are needed to dissect the roles of rare and structural variations.
Subject: SPINAL-CORD
DIAGNOSTIC-CRITERIA
SYNAPSE DEVELOPMENT
IRON HOMEOSTASIS
EKBOM DISEASE
BRAIN
PROTEIN
GENES
ORGANIZATION
NEUROGENESIS
3112 Neurosciences
3124 Neurology and psychiatry
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