TY - JOUR
T1 - GBA variants in REM sleep behavior disorder
T2 - A multicenter study
AU - Krohn, Lynne
AU - Ruskey, Jennifer A.
AU - Rudakou, Uladzislau
AU - Leveille, Etienne
AU - Asayesh, Farnaz
AU - Hu, Michele T.M.
AU - Arnulf, Isabelle
AU - Dauvilliers, Yves
AU - Högl, Birgit
AU - Stefani, Ambra
AU - Monaca, Christelle Charley
AU - Abril, Beatriz
AU - Plazzi, Giuseppe
AU - Antelmi, Elena
AU - Ferini-Strambi, Luigi
AU - Heidbreder, Anna
AU - Boeve, Bradley F.
AU - Espay, Alberto J.
AU - De Cock, Valérie Cochen
AU - Mollenhauer, Brit
AU - Sixel-Döring, Friederike
AU - Trenkwalder, Claudia
AU - Sonka, Karel
AU - Kemlink, David
AU - Figorilli, Michela
AU - Puligheddu, Monica
AU - Dijkstra, Femke
AU - Viaene, Mineke
AU - Oertel, Wolfgang
AU - Toffoli, Marco
AU - Gigli, Gian Luigi
AU - Valente, Mariarosaria
AU - Gagnon, Jean François
AU - Desautels, Alex
AU - Montplaisir, Jacques Y.
AU - Postuma, Ronald B.
AU - Rouleau, Guy A.
AU - Gan-Or, Ziv
N1 - Publisher Copyright:
© American Academy of Neurology.
PY - 2020/8/25
Y1 - 2020/8/25
N2 - 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.
AB - 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.
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U2 - 10.1212/WNL.0000000000010042
DO - 10.1212/WNL.0000000000010042
M3 - Article
C2 - 32591474
AN - SCOPUS:85089922704
SN - 0028-3878
VL - 95
SP - E1008-E1016
JO - Neurology
JF - Neurology
IS - 8
ER -