1. Large genome-wide association study identifies three novel risk variants for restless legs syndrome
- Author
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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, 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, and Public and occupational health
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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 - Abstract
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.
- Published
- 2020