ExomeChip-based rare variant association study in restless legs syndrome

Erik Tilch; Barbara Schormair; Chen Zhao; Birgit Högl; Ambra Stefani; Klaus Berger; Claudia Trenkwalder; Cornelius G. Bachmann; Magdolna Hornyak; Ingo Fietze; Martina Müller-Nurasyid; Annette Peters; Stefan Herms; Markus M. Nöthen; Bertram Müller-Myhsok; Konrad Oexle; Juliane Winkelmann

doi:10.1016/j.sleep.2022.04.001

ExomeChip-based rare variant association study in restless legs syndrome

Erik Tilch, Barbara Schormair, Chen Zhao, Birgit Högl, Ambra Stefani, Klaus Berger, Claudia Trenkwalder, Cornelius G. Bachmann, Magdolna Hornyak, Ingo Fietze, Martina Müller-Nurasyid, Annette Peters, Stefan Herms, Markus M. Nöthen, Bertram Müller-Myhsok, Konrad Oexle, Juliane Winkelmann

Research output: Contribution to journal › Article › peer-review

Abstract

Restless legs syndrome (RLS) is a common sleep-related movement disorder in populations of European descent and disease risk is strongly influenced by genetic factors. Common variants have been assessed extensively in several genome-wide association studies, but the contribution of rarer genetic variation has not been investigated at this scale. We therefore genotyped a case–control set of 9246 individuals for mainly rare and low frequency exonic variants using the Illumina ExomeChip. However, standard single variant and gene-level association tests were negative. This does not preclude a role of rare variants in RLS, but is likely due to the small sample size and the limited selection of rare genetic variation captured on the array. Therefore, exome or whole genome sequencing should be performed rather than increasing the sample size of ExomeChip studies in order to identify rare risk variants for RLS.

Original language	English
Pages (from-to)	26-30
Number of pages	5
Journal	Sleep Medicine
Volume	94
DOIs	https://doi.org/10.1016/j.sleep.2022.04.001
State	Published - Jun 2022
Externally published	Yes

Keywords

Genome-wide association study
RLS
Rare variant association study
Restless legs syndrome

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10.1016/j.sleep.2022.04.001

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Tilch, E., Schormair, B., Zhao, C., Högl, B., Stefani, A., Berger, K., Trenkwalder, C., Bachmann, C. G., Hornyak, M., Fietze, I., Müller-Nurasyid, M., Peters, A., Herms, S., Nöthen, M. M., Müller-Myhsok, B., Oexle, K., & Winkelmann, J. (2022). ExomeChip-based rare variant association study in restless legs syndrome. Sleep Medicine, 94, 26-30. https://doi.org/10.1016/j.sleep.2022.04.001

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title = "ExomeChip-based rare variant association study in restless legs syndrome",

abstract = "Restless legs syndrome (RLS) is a common sleep-related movement disorder in populations of European descent and disease risk is strongly influenced by genetic factors. Common variants have been assessed extensively in several genome-wide association studies, but the contribution of rarer genetic variation has not been investigated at this scale. We therefore genotyped a case–control set of 9246 individuals for mainly rare and low frequency exonic variants using the Illumina ExomeChip. However, standard single variant and gene-level association tests were negative. This does not preclude a role of rare variants in RLS, but is likely due to the small sample size and the limited selection of rare genetic variation captured on the array. Therefore, exome or whole genome sequencing should be performed rather than increasing the sample size of ExomeChip studies in order to identify rare risk variants for RLS.",

keywords = "Genome-wide association study, RLS, Rare variant association study, Restless legs syndrome",

author = "Erik Tilch and Barbara Schormair and Chen Zhao and Birgit H{\"o}gl and Ambra Stefani and Klaus Berger and Claudia Trenkwalder and Bachmann, {Cornelius G.} and Magdolna Hornyak and Ingo Fietze and Martina M{\"u}ller-Nurasyid and Annette Peters and Stefan Herms and N{\"o}then, {Markus M.} and Bertram M{\"u}ller-Myhsok and Konrad Oexle and Juliane Winkelmann",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

year = "2022",

month = jun,

doi = "10.1016/j.sleep.2022.04.001",

language = "English",

volume = "94",

pages = "26--30",

journal = "Sleep Medicine",

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Tilch, E, Schormair, B, Zhao, C, Högl, B, Stefani, A, Berger, K, Trenkwalder, C, Bachmann, CG, Hornyak, M, Fietze, I, Müller-Nurasyid, M, Peters, A, Herms, S, Nöthen, MM, Müller-Myhsok, B, Oexle, K & Winkelmann, J 2022, 'ExomeChip-based rare variant association study in restless legs syndrome', Sleep Medicine, vol. 94, pp. 26-30. https://doi.org/10.1016/j.sleep.2022.04.001

TY - JOUR

T1 - ExomeChip-based rare variant association study in restless legs syndrome

AU - Tilch, Erik

AU - Schormair, Barbara

AU - Zhao, Chen

AU - Högl, Birgit

AU - Stefani, Ambra

AU - Berger, Klaus

AU - Trenkwalder, Claudia

AU - Bachmann, Cornelius G.

AU - Hornyak, Magdolna

AU - Fietze, Ingo

AU - Müller-Nurasyid, Martina

AU - Peters, Annette

AU - Herms, Stefan

AU - Nöthen, Markus M.

AU - Müller-Myhsok, Bertram

AU - Oexle, Konrad

AU - Winkelmann, Juliane

PY - 2022/6

Y1 - 2022/6

N2 - Restless legs syndrome (RLS) is a common sleep-related movement disorder in populations of European descent and disease risk is strongly influenced by genetic factors. Common variants have been assessed extensively in several genome-wide association studies, but the contribution of rarer genetic variation has not been investigated at this scale. We therefore genotyped a case–control set of 9246 individuals for mainly rare and low frequency exonic variants using the Illumina ExomeChip. However, standard single variant and gene-level association tests were negative. This does not preclude a role of rare variants in RLS, but is likely due to the small sample size and the limited selection of rare genetic variation captured on the array. Therefore, exome or whole genome sequencing should be performed rather than increasing the sample size of ExomeChip studies in order to identify rare risk variants for RLS.

AB - Restless legs syndrome (RLS) is a common sleep-related movement disorder in populations of European descent and disease risk is strongly influenced by genetic factors. Common variants have been assessed extensively in several genome-wide association studies, but the contribution of rarer genetic variation has not been investigated at this scale. We therefore genotyped a case–control set of 9246 individuals for mainly rare and low frequency exonic variants using the Illumina ExomeChip. However, standard single variant and gene-level association tests were negative. This does not preclude a role of rare variants in RLS, but is likely due to the small sample size and the limited selection of rare genetic variation captured on the array. Therefore, exome or whole genome sequencing should be performed rather than increasing the sample size of ExomeChip studies in order to identify rare risk variants for RLS.

KW - Genome-wide association study

KW - RLS

KW - Rare variant association study

KW - Restless legs syndrome

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U2 - 10.1016/j.sleep.2022.04.001

DO - 10.1016/j.sleep.2022.04.001

M3 - Article

C2 - 35489115

AN - SCOPUS:85129002468

SN - 1389-9457

VL - 94

SP - 26

EP - 30

JO - Sleep Medicine

JF - Sleep Medicine

ER -

ExomeChip-based rare variant association study in restless legs syndrome

Abstract

Keywords

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