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

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  • Maria Didriksen
  • Muhammad Sulaman Nawaz
  • Joseph Dowsett
  • Steven Bell
  • Christian Erikstrup
  • Ole B Pedersen
  • Erik Sørensen
  • Poul J Jennum
  • Kristoffer S Burgdorf
  • Brendan Burchell
  • Adam S Butterworth
  • Nicole Soranzo
  • David B Rye
  • Lynn Marie Trotti
  • Prabhjyot Saini
  • Lilja Stefansdottir
  • Sigurdur H Magnusson
  • Gudmar Thorleifsson
  • Thordur Sigmundsson
  • Albert P Sigurdsson
  • Katja Van Den Hurk
  • Franke Quee
  • Michael W T Tanck
  • Willem H Ouwehand
  • David J Roberts
  • Eric J Earley
  • Michael P Busch
  • Alan E Mast
  • Grier P Page
  • John Danesh
  • Emanuele Di Angelantonio
  • Hreinn Stefansson
  • Henrik Ullum
  • Kari Stefansson
Vis graf over relationer

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.

OriginalsprogEngelsk
Artikelnummer703
TidsskriftCommunications biology
Vol/bind3
Udgave nummer1
Sider (fra-til)703
ISSN2399-3642
DOI
StatusUdgivet - 25 nov. 2020

ID: 61694334