Large genome-wide association study identifies three novel risk variants for restless legs syndrome

Autor: Thordur Sigmundsson, Erik Sørensen, David B. Rye, Katja van den Hurk, Franke A. Quee, Poul Jennum, Muhammad Nawaz, Willem H. Ouwehand, Michael W.T. Tanck, Steven Bell, Sigurdur H. Magnusson, Hreinn Stefansson, Gudmar Thorleifsson, Nicole Soranzo, Prabhjyot Saini, Maria Didriksen, Joseph Dowsett, Emanuele Di Angelantonio, Lynn Marie Trotti, Henrik Ullum, Eric J. Earley, Alan E. Mast, Michael P. Busch, David J. Roberts, Christian Erikstrup, Kari Stefansson, Kristoffer Sølvsten Burgdorf, Albert P. Sigurdsson, Ole Birger Pedersen, John Danesh, Grier P. Page, Lilja Stefansdottir, Brendan Burchell, Adam S. Butterworth
Přispěvatelé: Didriksen, Maria [0000-0002-4856-496X], Nawaz, Muhammad Sulaman [0000-0002-5576-9007], Dowsett, Joseph [0000-0001-5381-2633], Bell, Steven [0000-0001-6774-3149], Erikstrup, Christian [0000-0001-6551-6647], Pedersen, Ole B [0000-0003-2312-5976], Burchell, Brendan [0000-0002-8243-937X], Butterworth, Adam S [0000-0002-6915-9015], Tanck, Michael WT [0000-0001-9828-4459], Ouwehand, Willem H [0000-0002-7744-1790], Earley, Eric J [0000-0001-6576-1319], Busch, Michael P [0000-0002-1446-125X], Page, Grier P [0000-0003-2582-3786], Stefansson, Hreinn [0000-0002-9331-6666], Stefansson, Kari [0000-0003-1676-864X], Apollo - University of Cambridge Repository, Pedersen, Ole B. [0000-0003-2312-5976], Butterworth, Adam S. [0000-0002-6915-9015], Tanck, Michael W. T. [0000-0001-9828-4459], Ouwehand, Willem H. [0000-0002-7744-1790], Earley, Eric J. [0000-0001-6576-1319], Busch, Michael P. [0000-0002-1446-125X], Page, Grier P. [0000-0003-2582-3786], Epidemiology and Data Science, APH - Methodology, Public and occupational health
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Adult
medicine.medical_specialty
Linkage disequilibrium
QH301-705.5
692/617/375/1816
631/208/205/2138
Medicine (miscellaneous)
Genome-wide association study
Disease
Bioinformatics
Genome-wide association studies
Polymorphism
Single Nucleotide
General Biochemistry
Genetics and Molecular Biology
Linkage Disequilibrium
38
38/43
03 medical and health sciences
0302 clinical medicine
Restless Legs Syndrome
Epidemiology
38/23
mental disorders
medicine
Humans
Genetic Predisposition to Disease
Restless legs syndrome
Biology (General)
health care economics and organizations
Genetic association
Aged
business.industry
article
Sleep disorders
Middle Aged
medicine.disease
Obesity
631/208/199
030104 developmental biology
Meta-analysis
38/39
Gene expression
General Agricultural and Biological Sciences
business
030217 neurology & neurosurgery
Genome-Wide Association Study
Zdroj: Didriksen, M, Nawaz, M S, Dowsett, J, Bell, S, Erikstrup, C, Pedersen, O B, Sørensen, E, Jennum, P J, Burgdorf, K S, Burchell, B, Butterworth, A S, Soranzo, N, Rye, D B, Trotti, L M, Saini, P, Stefansdottir, L, Magnusson, S H, Thorleifsson, G, Sigmundsson, T, Sigurdsson, A P, Van Den Hurk, K, Quee, F, Tanck, M W T, Ouwehand, W H, Roberts, D J, Earley, E J, Busch, M P, Mast, A E, Page, G P, Danesh, J, Di Angelantonio, E, Stefansson, H, Ullum, H & Stefansson, K 2020, ' Large genome-wide association study identifies three novel risk variants for restless legs syndrome ', Communications Biology, vol. 3, no. 1, 703 . https://doi.org/10.1038/s42003-020-01430-1
Communications Biology, Vol 3, Iss 1, Pp 1-9 (2020)
Communications Biology
Communications Biology, 3(1):703. Springer Nature
ISSN: 2399-3642
DOI: 10.1038/s42003-020-01430-1
Popis: Funder: Scottish Government; doi: https://doi.org/10.13039/100012095
Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289
Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10−18), rs10068599-T (OR = 1.09, P = 6.9 × 10−10) and rs10769894-A (OR = 0.90, P = 9.4 × 10−14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed.
Databáze: OpenAIRE
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