GBA variants in REM sleep behavior disorder: A multicenter study

Lynne Krohn, Jennifer A. Ruskey, Uladzislau Rudakou, Etienne Leveille, Farnaz Asayesh, Michele T.M. Hu, Isabelle Arnulf, Yves Dauvilliers, Birgit Högl, Ambra Stefani, Christelle Charley Monaca, Beatriz Abril, Giuseppe Plazzi, Elena Antelmi, Luigi Ferini-Strambi, Anna Heidbreder, Bradley F. Boeve, Alberto J. Espay, Valérie Cochen De Cock, Brit MollenhauerFriederike Sixel-Döring, Claudia Trenkwalder, Karel Sonka, David Kemlink, Michela Figorilli, Monica Puligheddu, Femke Dijkstra, Mineke Viaene, Wolfgang Oertel, Marco Toffoli, Gian Luigi Gigli, Mariarosaria Valente, Jean François Gagnon, Alex Desautels, Jacques Y. Montplaisir, Ronald B. Postuma, Guy A. Rouleau, Ziv Gan-Or

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


ObjectiveTo study the role of GBA variants in the risk for isolated REM sleep behavior disorder (iRBD) and conversion to overt neurodegeneration.MethodsA total of 4,147 individuals were included: 1,061 patients with iRBD and 3,086 controls. GBA was fully sequenced using molecular inversion probes and Sanger sequencing. We analyzed the effects of GBA variants on the risk of iRBD, age at onset (AAO), and conversion rates.ResultsGBA variants were found in 9.5% of patients with iRBD compared to 4.1% of controls (odds ratio, 2.45; 95% confidence interval [CI], 1.87-3.22; p = 1 × 10-10). The estimated OR for mild p.N370S variant carriers was 3.69 (95% CI, 1.90-7.14; p = 3.5 × 10-5), while for severe variant carriers it was 17.55 (95% CI, 2.11-145.9; p = 0.0015). Carriers of severe GBA variants had an average AAO of 52.8 years, 7-8 years earlier than those with mild variants or noncarriers (p = 0.029). Of the GBA variant carriers with available data, 52.5% had converted, compared to 35.6% of noncarriers (p = 0.011), with a trend for faster conversion among severe GBA variant carriers. However, the results on AAO and conversion were based on small numbers and should be interpreted with caution.ConclusionsGBA variants robustly and differentially increase the risk of iRBD. The rate of conversion to neurodegeneration is also increased and may be faster among severe GBA variant carriers, although confirmation will be required in larger samples. Screening for RBD in healthy carriers of GBA variants should be studied as a potential way to identify GBA variant carriers who will develop a synucleinopathy in the future.

Original languageEnglish (US)
Pages (from-to)E1008-E1016
Issue number8
StatePublished - Aug 25 2020

ASJC Scopus subject areas

  • Clinical Neurology


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