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

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

doi:10.1038/s42003-020-01430-1

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

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 SigurdssonKatja 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

Abstract

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.

Originalsprog	Engelsk
Artikelnummer	703
Tidsskrift	Communications biology
Vol/bind	3
Udgave nummer	1
Sider (fra-til)	703
ISSN	2399-3642
DOI	https://doi.org/10.1038/s42003-020-01430-1
Status	Udgivet - 25 nov. 2020

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10.1038/s42003-020-01430-1

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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., ... Stefansson, K. (2020). Large genome-wide association study identifies three novel risk variants for restless legs syndrome. Communications biology, 3(1), 703. Artikel 703. https://doi.org/10.1038/s42003-020-01430-1

Didriksen, M, Nawaz, MS, Dowsett, J, Bell, S, Erikstrup, C, Pedersen, OB, Sørensen, E , Jennum, PJ, Burgdorf, KS, Burchell, B, Butterworth, AS, Soranzo, N, Rye, DB, Trotti, LM, Saini, P, Stefansdottir, L, Magnusson, SH, Thorleifsson, G, Sigmundsson, T, Sigurdsson, AP, Van Den Hurk, K, Quee, F, Tanck, MWT, Ouwehand, WH, Roberts, DJ, Earley, EJ, Busch, MP, Mast, AE, Page, GP, 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, bind 3, nr. 1, 703, s. 703. https://doi.org/10.1038/s42003-020-01430-1

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title = "Large genome-wide association study identifies three novel risk variants for restless legs syndrome",

abstract = "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.",

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

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doi = "10.1038/s42003-020-01430-1",

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T1 - Large genome-wide association study identifies three novel risk variants for restless legs syndrome

AU - Didriksen, Maria

AU - Nawaz, Muhammad Sulaman

AU - Dowsett, Joseph

AU - Bell, Steven

AU - Erikstrup, Christian

AU - Pedersen, Ole B

AU - Sørensen, Erik

AU - Jennum, Poul J

AU - Burgdorf, Kristoffer S

AU - Burchell, Brendan

AU - Butterworth, Adam S

AU - Soranzo, Nicole

AU - Rye, David B

AU - Trotti, Lynn Marie

AU - Saini, Prabhjyot

AU - Stefansdottir, Lilja

AU - Magnusson, Sigurdur H

AU - Thorleifsson, Gudmar

AU - Sigmundsson, Thordur

AU - Sigurdsson, Albert P

AU - Van Den Hurk, Katja

AU - Quee, Franke

AU - Tanck, Michael W T

AU - Ouwehand, Willem H

AU - Roberts, David J

AU - Earley, Eric J

AU - Busch, Michael P

AU - Mast, Alan E

AU - Page, Grier P

AU - Danesh, John

AU - Di Angelantonio, Emanuele

AU - Stefansson, Hreinn

AU - Ullum, Henrik

AU - Stefansson, Kari

PY - 2020/11/25

Y1 - 2020/11/25

N2 - 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.

AB - 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.

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U2 - 10.1038/s42003-020-01430-1

DO - 10.1038/s42003-020-01430-1

M3 - Journal article

C2 - 33239738

SN - 2399-3642

VL - 3

SP - 703

JO - Communications biology

JF - Communications biology

IS - 1

M1 - 703

ER -

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

Abstract

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