GBA1 rs3115534 Is Associated with REM Sleep Behavior Disorder in Parkinson's Disease in Nigerians

Background Rapid eye movement (REM) sleep behavior disorder (RBD) is an early feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Damaging coding variants in Glucocerebrosidase (GBA1) are a genetic risk factor for RBD. Recently, a population‐specific non‐coding risk variant...

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Published in:	Movement disorders Vol. 39; no. 4; pp. 728 - 733
Main Authors:	Crea, Peter Wild, Noyce, Alastair J., Kauffman, Marcelo, Tavadyan, Zaruhi, Hunter, Julie, Rentería, Miguel E., Koks, Sulev, Rieder, Carlos, Awad, Paula Saffie, Fon, Ted, Olguin, Patricio, Chan, Piu, Luo, Wei, Arboleda, Gonzalo, Hernandez, Alvaro, Salama, Mohamed, Westenberger, Ana, Illarionova, Anastasia, Hopfner, Franziska, Madoev, Harutyun, Junker, Johanna, Fang, Zih‐Hua, Xiromerisiou, Georgia, Dagklis, Ioannis, Stefanis, Leonidas, Medina, Alex, Divya, KP, Rajan, Roopa, Borgohain, Rupam, Salari, Mehri, Quattrone, Andrea, Hattori, Nobutaka, Shiraishi, Tomotaka, Krüger, Rejko, Ahmad‐Annuar, Azlina, Norlinah, Mohamed Ibrahim, Azmin, Shahrul, Lim, Shen‐Yang, Ojha, Rajeev, Okubadejo, Njideka, Cornejo‐Olivas, Mario, Rosales, Raymond, Iakovenko, Elena, Bardien, Soraya, Jeon, Beomseok, Cubo, Esther, Beyer, Katrin, Zweier, Christiane, Tinkhauser, Gerd, Lin, Chin‐Hsien, Amouri, Rim, Başak, A. Nazlı, Genc, Gencer, Çakmak, Özgür Öztop, Ertan, Sibel, Grosset, Donald, Morris, Huw R, Williams, Nigel, Lewis, Patrick Alfryn, Weil, Rimona, Stott, Simon, Jasaityte, Simona, Obese, Vida, Espay, Alberto, O'Grady, Alyssa, Fiske, Brian, Jonas, Cabell, Cruchaga, Carlos, Pantazis, Caroline B., Blauwendraat, Cornelis, Vitale, Dan, Mata, Ignacio F., Sarmiento, Ignacio Juan Keller, Kim, Jonggeol Jeff, Jankovic, Joseph, Murphy, Kaileigh, Kieburtz, Karl, Andersh, Kate, Markopoulou, Katerina, Levine, Kristin S., Ibanez, Laura, Marsili, Luca, Makarious, Mary B, Nalls, Mike A., Mencacci, Niccolò Emanuele, Albin, Roger, Chowdhury, Sohini, Foroud, Tatiana, Njideka, Okubadejo, Sani, Abubakar, Uchechi, Agulanna, Rufus, Akinyemi, Abiodun, Bello, Daniel, Ezuduemoih, Evewero, Ikwenu, Morenikeji, Komolafe, Paul, Nwani, Franscisca, Nwaokorie, Godwin, Osaigbovo, Simon, Ozomma
Format:	Journal Article
Language:	English
Published:	Hoboken, USA John Wiley & Sons, Inc 01-04-2024 Wiley Subscription Services, Inc
Subjects:	Behavior disorders Dementia disorders GBA1 genetics Glucosylceramidase Health risk assessment Lewy bodies Movement disorders Neurodegenerative diseases Nigerians Non-coding RNA Parkinson's disease REM sleep REM sleep behavior disorder Risk factors rs3115534 Sleep disorders GBA1 Parkinson's disease genetics rs3115534 Nigerians REM sleep behavior disorder
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Summary:	Background Rapid eye movement (REM) sleep behavior disorder (RBD) is an early feature of Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Damaging coding variants in Glucocerebrosidase (GBA1) are a genetic risk factor for RBD. Recently, a population‐specific non‐coding risk variant (rs3115534) was found to be associated with PD risk and earlier onset in individuals of African ancestry. Objectives We aimed to investigate whether the GBA1 rs3115534 PD risk variant is associated with RBD in persons with PD. Methods We studied 709 persons with PD and 776 neurologically healthy controls from Nigeria. All DNA samples were genotyped and imputed, and the GBA1 rs3115534 risk variant was extracted. The RBD screening questionnaire (RBDSQ) was used to assess symptoms of possible RBD. Results RBD was present in 200 PD (28.2%) and 51 (6.6%) controls. We identified that the non‐coding GBA1 rs3115534 risk variant is associated with possible RBD in individuals of Nigerian origin (β, 0.3640; standard error [SE], 0.103, P = 4.093e−04), as well as in all samples after adjusting for PD status (β, 0.2542; SE, 0.108; P = 0.019) suggesting that although non‐coding, this variant may have the same downstream consequences as GBA1 coding variants. Conclusions Our results indicate that the non‐coding GBA1 rs3115534 risk variant is associated with an increasing number of RBD symptoms in persons with PD of Nigerian origin. Further research is needed to assess if this variant is also associated with polysomnography‐defined RBD and with RBD symptoms in DLB. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Bibliography:	Funding for this study was provided by Global Parkinson's Genetics Program (GP2) through Aligning Science Across Parkinson's and implemented by The Michael J. Fox Foundation for Parkinson's Research. M.A.N.'s participation in this project was part of a competitive contract awarded to DataTecnica LLC by the National Institutes of Health to support open science research. S.B.‐C., M.R., A.S., A.N., C.B., and N.O. serve on the GP2 Steering Committee. Other authors have no conflicts to declare. Relevant conflicts of interest/financial disclosures Funding agencies ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0885-3185 1531-8257
DOI:	10.1002/mds.29753