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Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction. / Schormair, Barbara; Zhao, Chen; Bell, Steven; Didriksen, Maria; Nawaz, Muhammad S.; Schandra, Nathalie; Stefani, Ambra; Högl, Birgit; Dauvilliers, Yves; Bachmann, Cornelius G.; Kemlink, David; Sonka, Karel; Paulus, Walter; Trenkwalder, Claudia; Oertel, Wolfgang H.; Hornyak, Magdolna; Teder-Laving, Maris; Metspalu, Andres; Hadjigeorgiou, Georgios M.; Polo, Olli; Fietze, Ingo; Ross, Owen A.; Wszolek, Zbigniew K.; Ibrahim, Abubaker; Bergmann, Melanie; Kittke, Volker; Harrer, Philip; Dowsett, Joseph; Chenini, Sofiene; Ostrowski, Sisse Rye; Sørensen, Erik; Erikstrup, Christian; Pedersen, Ole B.; Topholm Bruun, Mie; Nielsen, Kaspar R.; Butterworth, Adam S.; Soranzo, Nicole; Ouwehand, Willem H.; Roberts, David J.; Danesh, John; Burchell, Brendan; Furlotte, Nicholas A.; Nandakumar, Priyanka; Earley, Christopher J.; Ondo, William G.; Xiong, Lan; Desautels, Alex; Perola, Markus; Vodicka, Pavel; Dina, Christian; Stoll, Monika; Franke, Andre; Lieb, Wolfgang; Stewart, Alexandre F R; Shah, Svati H; Gieger, Christian; Peters, Annette; Rye, David B.; Rouleau, Guy A; Berger, Klaus; Stefansson, Hreinn; Ullum, Henrik; Stefansson, Kari; Hinds, David A.; Di Angelantonio, Emanuele; Oexle, Konrad; Winkelmann, Juliane; 23andMe Research Team; D.E.S.I.R. study group.
In:
Nature Genetics, Vol. 56, No. 6, 2024, p. 1090-1099.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Schormair, B, Zhao, C, Bell, S
, Didriksen, M, Nawaz, MS, Schandra, N, Stefani, A, Högl, B, Dauvilliers, Y, Bachmann, CG, Kemlink, D, Sonka, K, Paulus, W, Trenkwalder, C, Oertel, WH, Hornyak, M, Teder-Laving, M, Metspalu, A, Hadjigeorgiou, GM, Polo, O, Fietze, I, Ross, OA, Wszolek, ZK, Ibrahim, A, Bergmann, M, Kittke, V, Harrer, P, Dowsett, J, Chenini, S
, Ostrowski, SR, Sørensen, E, Erikstrup, C
, Pedersen, OB, Topholm Bruun, M, Nielsen, KR, Butterworth, AS, Soranzo, N, Ouwehand, WH, Roberts, DJ, Danesh, J, Burchell, B, Furlotte, NA, Nandakumar, P, Earley, CJ, Ondo, WG, Xiong, L, Desautels, A, Perola, M, Vodicka, P, Dina, C, Stoll, M, Franke, A, Lieb, W, Stewart, AFR, Shah, SH, Gieger, C, Peters, A, Rye, DB, Rouleau, GA, Berger, K, Stefansson, H, Ullum, H, Stefansson, K, Hinds, DA, Di Angelantonio, E, Oexle, K, Winkelmann, J, 23andMe Research Team & D.E.S.I.R. study group 2024, '
Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction',
Nature Genetics, vol. 56, no. 6, pp. 1090-1099.
https://doi.org/10.1038/s41588-024-01763-1APA
Schormair, B., Zhao, C., Bell, S.
, Didriksen, M., Nawaz, M. S., Schandra, N., Stefani, A., Högl, B., Dauvilliers, Y., Bachmann, C. G., Kemlink, D., Sonka, K., Paulus, W., Trenkwalder, C., Oertel, W. H., Hornyak, M., Teder-Laving, M., Metspalu, A., Hadjigeorgiou, G. M., ... D.E.S.I.R. study group (2024).
Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.
Nature Genetics,
56(6), 1090-1099.
https://doi.org/10.1038/s41588-024-01763-1Vancouver
Schormair B, Zhao C, Bell S
, Didriksen M, Nawaz MS, Schandra N et al.
Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.
Nature Genetics. 2024;56(6):1090-1099.
https://doi.org/10.1038/s41588-024-01763-1Author
Schormair, Barbara ; Zhao, Chen ; Bell, Steven ; Didriksen, Maria ; Nawaz, Muhammad S. ; Schandra, Nathalie ; Stefani, Ambra ; Högl, Birgit ; Dauvilliers, Yves ; Bachmann, Cornelius G. ; Kemlink, David ; Sonka, Karel ; Paulus, Walter ; Trenkwalder, Claudia ; Oertel, Wolfgang H. ; Hornyak, Magdolna ; Teder-Laving, Maris ; Metspalu, Andres ; Hadjigeorgiou, Georgios M. ; Polo, Olli ; Fietze, Ingo ; Ross, Owen A. ; Wszolek, Zbigniew K. ; Ibrahim, Abubaker ; Bergmann, Melanie ; Kittke, Volker ; Harrer, Philip ; Dowsett, Joseph ; Chenini, Sofiene ; Ostrowski, Sisse Rye ; Sørensen, Erik ; Erikstrup, Christian ; Pedersen, Ole B. ; Topholm Bruun, Mie ; Nielsen, Kaspar R. ; Butterworth, Adam S. ; Soranzo, Nicole ; Ouwehand, Willem H. ; Roberts, David J. ; Danesh, John ; Burchell, Brendan ; Furlotte, Nicholas A. ; Nandakumar, Priyanka ; Earley, Christopher J. ; Ondo, William G. ; Xiong, Lan ; Desautels, Alex ; Perola, Markus ; Vodicka, Pavel ; Dina, Christian ; Stoll, Monika ; Franke, Andre ; Lieb, Wolfgang ; Stewart, Alexandre F R ; Shah, Svati H ; Gieger, Christian ; Peters, Annette ; Rye, David B. ; Rouleau, Guy A ; Berger, Klaus ; Stefansson, Hreinn ; Ullum, Henrik ; Stefansson, Kari ; Hinds, David A. ; Di Angelantonio, Emanuele ; Oexle, Konrad ; Winkelmann, Juliane ; 23andMe Research Team ; D.E.S.I.R. study group. / Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction. In: Nature Genetics. 2024 ; Vol. 56, No. 6. pp. 1090-1099.
Bibtex
@article{0dc9e81efa4d4f8f9d5a69e32a5c23ef,
title = "Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction",
abstract = "Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.",
author = "Barbara Schormair and Chen Zhao and Steven Bell and Maria Didriksen and Nawaz, {Muhammad S.} and Nathalie Schandra and Ambra Stefani and Birgit H{\"o}gl and Yves Dauvilliers and Bachmann, {Cornelius G.} and David Kemlink and Karel Sonka and Walter Paulus and Claudia Trenkwalder and Oertel, {Wolfgang H.} and Magdolna Hornyak and Maris Teder-Laving and Andres Metspalu and Hadjigeorgiou, {Georgios M.} and Olli Polo and Ingo Fietze and Ross, {Owen A.} and Wszolek, {Zbigniew K.} and Abubaker Ibrahim and Melanie Bergmann and Volker Kittke and Philip Harrer and Joseph Dowsett and Sofiene Chenini and Ostrowski, {Sisse Rye} and Erik S{\o}rensen and Christian Erikstrup and Pedersen, {Ole B.} and {Topholm Bruun}, Mie and Nielsen, {Kaspar R.} and Butterworth, {Adam S.} and Nicole Soranzo and Ouwehand, {Willem H.} and Roberts, {David J.} and John Danesh and Brendan Burchell and Furlotte, {Nicholas A.} and Priyanka Nandakumar and Earley, {Christopher J.} and Ondo, {William G.} and Lan Xiong and Alex Desautels and Markus Perola and Pavel Vodicka and Christian Dina and Monika Stoll and Andre Franke and Wolfgang Lieb and Stewart, {Alexandre F R} and Shah, {Svati H} and Christian Gieger and Annette Peters and Rye, {David B.} and Rouleau, {Guy A} and Klaus Berger and Hreinn Stefansson and Henrik Ullum and Kari Stefansson and Hinds, {David A.} and {Di Angelantonio}, Emanuele and Konrad Oexle and Juliane Winkelmann and {23andMe Research Team} and {D.E.S.I.R. study group}",
note = "Publisher Copyright: {\textcopyright} 2024. The Author(s).",
year = "2024",
doi = "10.1038/s41588-024-01763-1",
language = "English",
volume = "56",
pages = "1090--1099",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "6",
}
RIS
TY - JOUR
T1 - Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction
AU - Schormair, Barbara
AU - Zhao, Chen
AU - Bell, Steven
AU - Didriksen, Maria
AU - Nawaz, Muhammad S.
AU - Schandra, Nathalie
AU - Stefani, Ambra
AU - Högl, Birgit
AU - Dauvilliers, Yves
AU - Bachmann, Cornelius G.
AU - Kemlink, David
AU - Sonka, Karel
AU - Paulus, Walter
AU - Trenkwalder, Claudia
AU - Oertel, Wolfgang H.
AU - Hornyak, Magdolna
AU - Teder-Laving, Maris
AU - Metspalu, Andres
AU - Hadjigeorgiou, Georgios M.
AU - Polo, Olli
AU - Fietze, Ingo
AU - Ross, Owen A.
AU - Wszolek, Zbigniew K.
AU - Ibrahim, Abubaker
AU - Bergmann, Melanie
AU - Kittke, Volker
AU - Harrer, Philip
AU - Dowsett, Joseph
AU - Chenini, Sofiene
AU - Ostrowski, Sisse Rye
AU - Sørensen, Erik
AU - Erikstrup, Christian
AU - Pedersen, Ole B.
AU - Topholm Bruun, Mie
AU - Nielsen, Kaspar R.
AU - Butterworth, Adam S.
AU - Soranzo, Nicole
AU - Ouwehand, Willem H.
AU - Roberts, David J.
AU - Danesh, John
AU - Burchell, Brendan
AU - Furlotte, Nicholas A.
AU - Nandakumar, Priyanka
AU - Earley, Christopher J.
AU - Ondo, William G.
AU - Xiong, Lan
AU - Desautels, Alex
AU - Perola, Markus
AU - Vodicka, Pavel
AU - Dina, Christian
AU - Stoll, Monika
AU - Franke, Andre
AU - Lieb, Wolfgang
AU - Stewart, Alexandre F R
AU - Shah, Svati H
AU - Gieger, Christian
AU - Peters, Annette
AU - Rye, David B.
AU - Rouleau, Guy A
AU - Berger, Klaus
AU - Stefansson, Hreinn
AU - Ullum, Henrik
AU - Stefansson, Kari
AU - Hinds, David A.
AU - Di Angelantonio, Emanuele
AU - Oexle, Konrad
AU - Winkelmann, Juliane
AU - 23andMe Research Team
AU - D.E.S.I.R. study group
N1 - Publisher Copyright:
© 2024. The Author(s).
PY - 2024
Y1 - 2024
N2 - Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.
AB - Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.
U2 - 10.1038/s41588-024-01763-1
DO - 10.1038/s41588-024-01763-1
M3 - Journal article
C2 - 38839884
AN - SCOPUS:85196230476
VL - 56
SP - 1090
EP - 1099
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 6
ER -
