Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder
Kheireddin Mufti
(1)
,
Eric Yu
(2)
,
Uladzislau Rudakou
(2)
,
Lynne Krohn
(3)
,
Jennifer A Ruskey
(4)
,
Farnaz Asayesh
(4)
,
Sandra B Laurent
(2)
,
Dan Spiegelman
(4)
,
Isabelle Arnulf
(5)
,
Jacques y Montplaisir
(6)
,
Jean-François Gagnon
(7)
,
Alex Desautels
(7)
,
Yves Dauvilliers
(5)
,
Gian Luigi Gigli
(8)
,
Mariarosaria Valente
(8)
,
Francesco Janes
(8)
,
Andrea Bernardini
(9)
,
Birgit Högl
(10)
,
Ambra Stefani
(10)
,
Evi Holzknecht
(10)
,
Karel Sonka
(11)
,
David Kemlink
(12)
,
Wolfgang Oertel
(13)
,
Annette Janzen
(13)
,
Giuseppe Plazzi
(14)
,
Elena Antelmi
(14)
,
Michela Figorilli
(15)
,
Monica Puligheddu
(15)
,
Brit Mollenhauer
(16)
,
Claudia Trenkwalder
(17)
,
Friederike Sixel-Döring
(18)
,
Valérie Cochen de Cock
(19, 20)
,
Christelle Charley Monaca
(21)
,
Anna Heidbreder
(22)
,
Luigi Ferini-Strambi
(23)
,
Femke Dijkstra
(24)
,
Mineke Viaene
(24)
,
Beatriz Abril
(25)
,
Bradley F Boeve
(26)
,
Jean-François Trempe
(3)
,
Guy A Rouleau
(27)
,
Ronald B Postuma
(28)
,
Ziv Gan-Or
(29)
1
ICM -
Institut du Cerveau = Paris Brain Institute
2 Montreal Neurological Institute and Hospital
3 McGill University = Université McGill [Montréal, Canada]
4 Department of Neurology and Neurosurgery [Montreal]
5 Service de Pathologies du sommeil [CHU Pitié-Salpêtrière]
6 UQAM - Université du Québec à Montréal = University of Québec in Montréal
7 CEAMS - Centre d'études avancées en Médecine du Sommeil
8 Università degli Studi di Udine - University of Udine [Italie]
9 Università degli Studi di Milano, IRCCS Policlinico San Donato
10 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
11 Medicine Charles University and General Faculty Hospital in Prague
12 First Faculty of Medicine Charles University [Prague]
13 Philipps Universität Marburg = Philipps University of Marburg
14 University of Bologna/Università di Bologna
15 UniCa - Università degli Studi di Cagliari = University of Cagliari
16 Department of Soil Science of Temperate Ecosystems, Georg August University of Goettingen, Buesgenweg 2, 37077, Goettingen, Germany
17 Georg-August-University = Georg-August-Universität Göttingen
18 Paracelsus-Elena-Klinik, Kassel, Germany.
19 Service de Neurologie [CHU Saint-Antoine]
20 Euromov DHM - EuroMov - Digital Health in Motion
21 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
22 UKM - University Hospital Münster - Universitaetsklinikum Muenster [Germany]
23 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
24 Jessa Ziekenhuis [Hasselt]
25 UGR - Universidad de Granada = University of Granada
26 Mayo Clinic
27 CHU Sainte Justine [Montréal]
28 Montreal General Hospital
29 NIH - National Institutes of Health [Bethesda]
2 Montreal Neurological Institute and Hospital
3 McGill University = Université McGill [Montréal, Canada]
4 Department of Neurology and Neurosurgery [Montreal]
5 Service de Pathologies du sommeil [CHU Pitié-Salpêtrière]
6 UQAM - Université du Québec à Montréal = University of Québec in Montréal
7 CEAMS - Centre d'études avancées en Médecine du Sommeil
8 Università degli Studi di Udine - University of Udine [Italie]
9 Università degli Studi di Milano, IRCCS Policlinico San Donato
10 IMU - Innsbruck Medical University = Medizinische Universität Innsbruck
11 Medicine Charles University and General Faculty Hospital in Prague
12 First Faculty of Medicine Charles University [Prague]
13 Philipps Universität Marburg = Philipps University of Marburg
14 University of Bologna/Università di Bologna
15 UniCa - Università degli Studi di Cagliari = University of Cagliari
16 Department of Soil Science of Temperate Ecosystems, Georg August University of Goettingen, Buesgenweg 2, 37077, Goettingen, Germany
17 Georg-August-University = Georg-August-Universität Göttingen
18 Paracelsus-Elena-Klinik, Kassel, Germany.
19 Service de Neurologie [CHU Saint-Antoine]
20 Euromov DHM - EuroMov - Digital Health in Motion
21 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
22 UKM - University Hospital Münster - Universitaetsklinikum Muenster [Germany]
23 UniSR - Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie]
24 Jessa Ziekenhuis [Hasselt]
25 UGR - Universidad de Granada = University of Granada
26 Mayo Clinic
27 CHU Sainte Justine [Montréal]
28 Montreal General Hospital
29 NIH - National Institutes of Health [Bethesda]
Uladzislau Rudakou
- Function : Author
- PersonId : 800395
- ORCID : 0000-0002-1411-7985
Lynne Krohn
- Function : Author
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- ORCID : 0000-0001-6554-1666
Isabelle Arnulf
- Function : Author
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- IdRef : 078091179
Alex Desautels
- Function : Author
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- ORCID : 0000-0002-2495-5675
Yves Dauvilliers
- Function : Author
- PersonId : 758941
- ORCID : 0000-0003-0683-6506
Mariarosaria Valente
- Function : Author
- PersonId : 807690
- ORCID : 0000-0001-6077-1315
Ambra Stefani
- Function : Author
- PersonId : 791695
- ORCID : 0000-0003-4259-8824
Karel Sonka
- Function : Author
- PersonId : 763639
- ORCID : 0000-0001-5773-9656
David Kemlink
- Function : Author
- PersonId : 763638
- ORCID : 0000-0003-1398-5796
Giuseppe Plazzi
- Function : Author
- PersonId : 767723
- ORCID : 0000-0001-6937-3065
Elena Antelmi
- Function : Author
- PersonId : 791033
- ORCID : 0000-0003-1739-6139
Michela Figorilli
- Function : Author
- PersonId : 785857
- ORCID : 0000-0002-1638-1384
Monica Puligheddu
- Function : Author
- PersonId : 785858
- ORCID : 0000-0002-6837-6608
Brit Mollenhauer
- Function : Author
- PersonId : 792182
- ORCID : 0000-0001-8437-3645
Valérie Cochen de Cock
- Function : Author
- PersonId : 1136432
- IdHAL : valerie-cochen
- ORCID : 0000-0002-6460-4319
Anna Heidbreder
- Function : Author
- PersonId : 791697
- ORCID : 0000-0002-9552-7619
Luigi Ferini-Strambi
- Function : Author
- PersonId : 791696
- ORCID : 0000-0003-2867-5424
Femke Dijkstra
- Function : Author
- PersonId : 807692
- ORCID : 0000-0002-8621-977X
Mineke Viaene
- Function : Author
- PersonId : 807693
- ORCID : 0000-0003-3702-106X
Guy A Rouleau
- Function : Author
- PersonId : 764544
- ORCID : 0000-0001-8403-1418
Abstract
Objective
To examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated REM sleep behavior disorder (iRBD).
Methods
We fully sequenced 25 genes previously identified in GWASs of PD in a total of 1,039 patients with iRBD and 1,852 controls. The role of rare heterozygous variants in these genes was examined with burden tests. The contribution of biallelic variants was further tested. To examine the potential effect of rare nonsynonymous BST1 variants on the protein structure, we performed in silico structural analysis. Finally, we examined the association of common variants using logistic regression adjusted for age and sex.
Results
We found an association between rare heterozygous nonsynonymous variants in BST1 and iRBD (p = 0.0003 at coverage >50× and 0.0004 at >30×), driven mainly by 3 nonsynonymous variants (p.V85M, p.I101V, and p.V272M) found in 22 (1.2%) controls vs 2 (0.2%) patients. All 3 variants seem to be loss-of-function variants with a potential effect on the protein structure and stability. Rare noncoding heterozygous variants in LAMP3 were also associated with iRBD (p = 0.0006 at >30×). We found no association between rare heterozygous variants in the rest of genes and iRBD. Several carriers of biallelic variants were identified, yet there was no overrepresentation in iRBD.
Conclusion
Our results suggest that rare coding variants in BST1 and rare noncoding variants in LAMP3 are associated with iRBD. Additional studies are required to replicate these results and to examine whether loss of function of BST1 could be a therapeutic target.
Origin : Publication funded by an institution