Cargando…
Large genome-wide association study identifies three novel risk variants for restless legs syndrome
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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2020
|
| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689502/ https://www.ncbi.nlm.nih.gov/pubmed/33239738 http://dx.doi.org/10.1038/s42003-020-01430-1 |
| _version_ | 1783613874924158976 |
|---|---|
| author | Didriksen, Maria Nawaz, Muhammad Sulaman Dowsett, Joseph Bell, Steven Erikstrup, Christian Pedersen, Ole B. Sørensen, Erik Jennum, Poul J. Burgdorf, Kristoffer S. Burchell, Brendan Butterworth, Adam S. Soranzo, Nicole Rye, David B. Trotti, Lynn Marie Saini, Prabhjyot Stefansdottir, Lilja Magnusson, Sigurdur H. Thorleifsson, Gudmar Sigmundsson, Thordur Sigurdsson, Albert P. Van Den Hurk, Katja Quee, Franke Tanck, Michael W. T. Ouwehand, Willem H. Roberts, David J. Earley, Eric J. Busch, Michael P. Mast, Alan E. Page, Grier P. Danesh, John Di Angelantonio, Emanuele Stefansson, Hreinn Ullum, Henrik Stefansson, Kari |
| author_facet | Didriksen, Maria Nawaz, Muhammad Sulaman Dowsett, Joseph Bell, Steven Erikstrup, Christian Pedersen, Ole B. Sørensen, Erik Jennum, Poul J. Burgdorf, Kristoffer S. Burchell, Brendan Butterworth, Adam S. Soranzo, Nicole Rye, David B. Trotti, Lynn Marie Saini, Prabhjyot Stefansdottir, Lilja Magnusson, Sigurdur H. Thorleifsson, Gudmar Sigmundsson, Thordur Sigurdsson, Albert P. Van Den Hurk, Katja Quee, Franke Tanck, Michael W. T. Ouwehand, Willem H. Roberts, David J. Earley, Eric J. Busch, Michael P. Mast, Alan E. Page, Grier P. Danesh, John Di Angelantonio, Emanuele Stefansson, Hreinn Ullum, Henrik Stefansson, Kari |
| author_sort | Didriksen, Maria |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-7689502 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2020 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-76895022020-11-30 Large genome-wide association study identifies three novel risk variants for restless legs syndrome Didriksen, Maria Nawaz, Muhammad Sulaman Dowsett, Joseph Bell, Steven Erikstrup, Christian Pedersen, Ole B. Sørensen, Erik Jennum, Poul J. Burgdorf, Kristoffer S. Burchell, Brendan Butterworth, Adam S. Soranzo, Nicole Rye, David B. Trotti, Lynn Marie Saini, Prabhjyot Stefansdottir, Lilja Magnusson, Sigurdur H. Thorleifsson, Gudmar Sigmundsson, Thordur Sigurdsson, Albert P. Van Den Hurk, Katja Quee, Franke Tanck, Michael W. T. Ouwehand, Willem H. Roberts, David J. Earley, Eric J. Busch, Michael P. Mast, Alan E. Page, Grier P. Danesh, John Di Angelantonio, Emanuele Stefansson, Hreinn Ullum, Henrik Stefansson, Kari Commun Biol Article 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. Nature Publishing Group UK 2020-11-25 /pmc/articles/PMC7689502/ /pubmed/33239738 http://dx.doi.org/10.1038/s42003-020-01430-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article Didriksen, Maria Nawaz, Muhammad Sulaman Dowsett, Joseph Bell, Steven Erikstrup, Christian Pedersen, Ole B. Sørensen, Erik Jennum, Poul J. Burgdorf, Kristoffer S. Burchell, Brendan Butterworth, Adam S. Soranzo, Nicole Rye, David B. Trotti, Lynn Marie Saini, Prabhjyot Stefansdottir, Lilja Magnusson, Sigurdur H. Thorleifsson, Gudmar Sigmundsson, Thordur Sigurdsson, Albert P. Van Den Hurk, Katja Quee, Franke Tanck, Michael W. T. Ouwehand, Willem H. Roberts, David J. Earley, Eric J. Busch, Michael P. Mast, Alan E. Page, Grier P. Danesh, John Di Angelantonio, Emanuele Stefansson, Hreinn Ullum, Henrik Stefansson, Kari Large genome-wide association study identifies three novel risk variants for restless legs syndrome |
| title | Large genome-wide association study identifies three novel risk variants for restless legs syndrome |
| title_full | Large genome-wide association study identifies three novel risk variants for restless legs syndrome |
| title_fullStr | Large genome-wide association study identifies three novel risk variants for restless legs syndrome |
| title_full_unstemmed | Large genome-wide association study identifies three novel risk variants for restless legs syndrome |
| title_short | Large genome-wide association study identifies three novel risk variants for restless legs syndrome |
| title_sort | large genome-wide association study identifies three novel risk variants for restless legs syndrome |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689502/ https://www.ncbi.nlm.nih.gov/pubmed/33239738 http://dx.doi.org/10.1038/s42003-020-01430-1 |
| work_keys_str_mv | AT didriksenmaria largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT nawazmuhammadsulaman largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT dowsettjoseph largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT bellsteven largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT erikstrupchristian largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT pedersenoleb largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT sørensenerik largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT jennumpoulj largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT burgdorfkristoffers largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT burchellbrendan largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT butterworthadams largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT soranzonicole largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT ryedavidb largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT trottilynnmarie largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT sainiprabhjyot largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT stefansdottirlilja largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT magnussonsigurdurh largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT thorleifssongudmar largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT sigmundssonthordur largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT sigurdssonalbertp largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT vandenhurkkatja largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT queefranke largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT tanckmichaelwt largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT ouwehandwillemh largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT robertsdavidj largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT earleyericj largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT buschmichaelp largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT mastalane largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT pagegrierp largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT daneshjohn largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT diangelantonioemanuele largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT stefanssonhreinn largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT ullumhenrik largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome AT stefanssonkari largegenomewideassociationstudyidentifiesthreenovelriskvariantsforrestlesslegssyndrome |