Abstract
Background: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). Objective: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. Methods: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. Results: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. Conclusion: Our results do not support a major role for variants in these genes in the risk of iRBD.
| Original language | English |
|---|---|
| Pages (from-to) | 235-240 |
| Number of pages | 6 |
| Journal | Movement Disorders |
| Volume | 36 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2021 |
Keywords
- REM sleep behavior disorder; genetic analysis; Parkinson's disease
ASJC Scopus subject areas
- Neurology
- Clinical Neurology
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Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder. / Mufti, Kheireddin; Rudakou, Uladzislau; Yu, Eric; Krohn, Lynne; Ruskey, Jennifer A.; Asayesh, Farnaz; Laurent, Sandra B.; Spiegelman, Dan; Arnulf, Isabelle; Hu, Michele T.M.; Montplaisir, Jacques Y.; Gagnon, Jean François; Desautels, Alex; Dauvilliers, Yves; Gigli, Gian Luigi; Valente, Mariarosaria; Janes, Francesco; Högl, Birgit; Stefani, Ambra; Holzknecht, Evi; Šonka, Karel; Kemlink, David; Oertel, Wolfgang; Janzen, Annette; Plazzi, Giuseppe; Antelmi, Elena; Figorilli, Michela; Puligheddu, Monica; Mollenhauer, Brit; Trenkwalder, Claudia; Sixel-Döring, Friederike; Cochen De Cock, Valérie; Monaca, Christelle Charley; Heidbreder, Anna; Ferini-Strambi, Luigi; Dijkstra, Femke; Viaene, Mineke; Abril, Beatriz; Boeve, Bradley F.; Postuma, Ronald B.; Rouleau, Guy A.; Gan-Or, Ziv.
In: Movement Disorders, Vol. 36, No. 1, 01.2021, p. 235-240.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Comprehensive Analysis of Familial Parkinsonism Genes in Rapid-Eye-Movement Sleep Behavior Disorder
AU - Mufti, Kheireddin
AU - Rudakou, Uladzislau
AU - Yu, Eric
AU - Krohn, Lynne
AU - Ruskey, Jennifer A.
AU - Asayesh, Farnaz
AU - Laurent, Sandra B.
AU - Spiegelman, Dan
AU - Arnulf, Isabelle
AU - Hu, Michele T.M.
AU - Montplaisir, Jacques Y.
AU - Gagnon, Jean François
AU - Desautels, Alex
AU - Dauvilliers, Yves
AU - Gigli, Gian Luigi
AU - Valente, Mariarosaria
AU - Janes, Francesco
AU - Högl, Birgit
AU - Stefani, Ambra
AU - Holzknecht, Evi
AU - Šonka, Karel
AU - Kemlink, David
AU - Oertel, Wolfgang
AU - Janzen, Annette
AU - Plazzi, Giuseppe
AU - Antelmi, Elena
AU - Figorilli, Michela
AU - Puligheddu, Monica
AU - Mollenhauer, Brit
AU - Trenkwalder, Claudia
AU - Sixel-Döring, Friederike
AU - Cochen De Cock, Valérie
AU - Monaca, Christelle Charley
AU - Heidbreder, Anna
AU - Ferini-Strambi, Luigi
AU - Dijkstra, Femke
AU - Viaene, Mineke
AU - Abril, Beatriz
AU - Boeve, Bradley F.
AU - Postuma, Ronald B.
AU - Rouleau, Guy A.
AU - Gan-Or, Ziv
N1 - Funding Information: This work was financially supported by the Michael J. Fox Foundation; the Canadian Consortium on Neurodegeneration in Aging (CCNA); Parkinson Canada; and the Canada First Research Excellence Fund (CFREF), awarded to McGill University for the Healthy Brains for Healthy Lives (HBHL) program. The Montreal cohort was funded by the Canadian Institutes of Health Research (CIHR) and the W. Garfield Weston Foundation. The Oxford Discovery study was funded by the Monument Trust Discovery Award from Parkinson's UK and supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre based at Oxford University Hospitals NHS Trust and University of Oxford, the NIHR Clinical Research Network and the Dementias and Neurodegenerative Diseases Research Network (DeNDRoN). Funding agencies: Funding Information: J.‐F.G. holds a Canada Research Chair in cognitive decline in pathological aging. W.O. is Hertie senior research professor, supported by the Hertie Foundation. E.A.F. holds a Canada Research Chair (Tier 1) in PD. G.A.R. holds a Canada Research Chair (Tier 1) in genetics of the nervous system and the Wilder Penfield Chair in neurosciences. Z.G.‐O. is supported by the Fonds de recherche du Québec–Santé Chercheur‐Boursier award and is a Parkinson Canada New Investigator awardee. We thank the participants for their contribution to the study. We thank D. Rochefort, H. Catoire, and V. Zaharieva for their assistance. Funding Information: Kheireddin Mufti reports no conflict of interests to disclose. Uladzislau Rudakou reports no conflict of interest to disclose. Eric Yu reports no conflict of interests to disclose. Lynne Krohn reports no conflict of interests to disclose. Jennifer A. Ruskey reports no conflict of interests to disclose. Farnaz Asayesh reports no conflict of interests to disclose. Sandra B. Laurent reports no conflict of interests to disclose. Dan Spiegelman reports no conflict of interests to disclose. Isabelle Arnulf received fees for speaking engagements from UCB pharma, consultancy for Roche, Novartis, and Ono Pharma. Michele T.M. Hu received consultancy fees from Roche and Biogen Pharmaceuticals. Jacques Y. Montplaisir received consultancy fees from Eisai Co. Jean‐François Gagnon reports research funding from the Canadian Institutes of Health Research (CIHR). Alex Desautels received grants from Flamel Ireland, Pfizer, Biron, and Canopy Growth, as well as fees for speaking engagements from Biogen and from UCB pharma. Yves Dauvilliers reports no conflict of interests to disclose. Gian Luigi Gigli reports no conflict of interests to disclose. Mariarosaria Valente reports no conflict of interests to disclose. Francesco Janes reports no conflict of interests to disclose. Birgit Högl received consultancy fees from Axovant, BenevolentBio, Takeda, Roche, and Ono and received speaker honoraria from Eli Lilly, Mundipharma, UCB, AbbVie, Inspire, and Lundbeck. Ambra Stefani reports no conflict of interests to disclose. Evi Holzknecht reports no conflict of interests to disclose. Karel Sonka reports no conflict of interests to disclose. David Kemlink reports no conflict of interests to disclose. Wolfgang Oertel reports no conflict of interests related to the study. He received consultancy or speaker fees from Adamas, AbbVie, Desitin, Novartis, and Roche. He has received research funding from the Deutsche Forschungsgemeinschaft (DFG), EU (Horizon2020), Parkinson Fonds Deutschland, Deutsche Parkinson Vereinigung, and Roche Pharma, Basel, Switzerland. Annette Janzen reports no conflict of interests to disclose. She has received research funding from Parkinson Fonds Deutschland. Giuseppe Plazzi reports no conflict of interests to disclose. Elena Antelmi reports no conflict of interests to disclose. Michela Figorilli reports no conflict of interests to disclose. Monica Puligheddu reports no conflict of interests to disclose. Brit Mollenhauer (BM) has received honoraria for consultancy from Roche, Biogen, UCB, and Sun Pharma Advanced Research Company. BM is member of the executive steering committee of the Parkinson Progression Marker Initiative and principle investigator of the Systemic Synuclein Sampling Study of the Michael J. Fox Foundation for Parkinson's Research and has received research funding from the Deutsche Forschungsgemeinschaft (DFG), EU (Horizon2020), Parkinson Fonds Deutschland, Deutsche Parkinson Vereinigung, and the Michael J. Fox Foundation for Parkinson's Research. Claudia Trenkwalder received honoraria for lectures from UCB, Grünenthal, and Otsuka and consultancy fees from Britannia Pharmaceuticals and Roche. Friederike Sixel‐Döring received honoraria for lectures from Abbott, Desitin, Grünenthal, Licher MT, STADA Pharm, and UCB and seminar fees from Boston Scientific and Licher MT. Friederike Sixel‐Döring serves on the advisory board for STADA Pharm and has no conflict of interest with the presented study. Valérie Cochen De Cock reports no conflict of interests to disclose. Christelle Charley Monaca reports no conflict of interests to disclose. Anna Heidbreder reports no conflict of interests to disclose. Luigi Ferini‐Strambi reports no conflict of interests to disclose. Femke Dijkstra reports no conflict of interests to disclose. Mineke Viaene reports no conflict of interests to disclose. Beatriz Abril reports no conflict of interests to disclose. Bradley F. Boeve has served as an investigator for clinical trials sponsored by Biogen and Alector. He serves on the scientific advisory board of the Tau Consortium. He receives research support from the NIH, the Mayo Clinic Dorothy and Harry T. Mangurian Jr. Lewy Body Dementia Program, the Little Family Foundation, and the LBD Functional Genomics Program. Ronald B. Postuma reports grants and Fonds de la Recherche en Sante, as well as grants from the Canadian Institute of Health Research, The Parkinson Society of Canada, the WestonGarfield Foundation, the Michael J. Fox Foundation, and the Webster Foundation, as well as personal fees from Takeda, Roche, Teva Neurosciences, Novartis Canada, Biogen, Boehringer Ingelheim, Theranexus, GE HealthCare, Jazz Pharmaceuticals, AbbVie, Jannsen, Otsuko, Phytopharmics, and Inception Sciences. Guy A. Rouleau reports no conflict of interests to disclose. Ziv Gan‐Or received consultancy fees from Lysosomal Therapeutics Inc. (LTI), Idorsia, Prevail Therapeutics, Inceptions Sciences (now Ventus), Ono Therapeutics, Denali, Handl Therapeutics, Neuron23, and Deerfield. Publisher Copyright: © 2020 International Parkinson and Movement Disorder Society Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - Background: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). Objective: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. Methods: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. Results: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. Conclusion: Our results do not support a major role for variants in these genes in the risk of iRBD.
AB - Background: There is only partial overlap in the genetic background of isolated rapid-eye-movement sleep behavior disorder (iRBD) and Parkinson's disease (PD). Objective: To examine the role of autosomal dominant and recessive PD or atypical parkinsonism genes in the risk of iRBD. Methods: Ten genes, comprising the recessive genes PRKN, DJ-1 (PARK7), PINK1, VPS13C, ATP13A2, FBXO7, and PLA2G6 and the dominant genes LRRK2, GCH1, and VPS35, were fully sequenced in 1039 iRBD patients and 1852 controls of European ancestry, followed by association tests. Results: We found no association between rare heterozygous variants in the tested genes and risk of iRBD. Several homozygous and compound heterozygous carriers were identified, yet there was no overrepresentation in iRBD patients versus controls. Conclusion: Our results do not support a major role for variants in these genes in the risk of iRBD.
KW - REM sleep behavior disorder; genetic analysis; Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=85091797307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85091797307&partnerID=8YFLogxK
U2 - 10.1002/mds.28318
DO - 10.1002/mds.28318
M3 - Article
C2 - 33001463
AN - SCOPUS:85091797307
VL - 36
SP - 235
EP - 240
JO - Movement Disorders
JF - Movement Disorders
SN - 0885-3185
IS - 1
ER -