RT Journal Article
SR Electronic
T1 Novel Associations of <em>BST1</em> and <em>LAMP3</em> with Rapid Eye Movement Sleep Behavior Disorder
JF Neurology
JO Neurology
FD Lippincott Williams &amp; Wilkins
SP 10.1212/WNL.0000000000011464
DO 10.1212/WNL.0000000000011464
A1 Mufti, Kheireddin
A1 Yu, Eric
A1 Rudakou, Uladzislau
A1 Krohn, Lynne
A1 Ruskey, Jennifer A.
A1 Asayesh, Farnaz
A1 Laurent, Sandra B.
A1 Spiegelman, Dan
A1 Arnulf, Isabelle
A1 Hu, Michele T.M.
A1 Montplaisir, Jacques Y.
A1 Gagnon, Jean-François
A1 Desautels, Alex
A1 Dauvilliers, Yves
A1 Gigli, Gian Luigi
A1 Valente, Mariarosaria
A1 Janes, Francesco
A1 Bernardini, Andrea
A1 Högl, Birgit
A1 Stefani, Ambra
A1 Holzknecht, Evi
A1 Sonka, Karel
A1 Kemlink, David
A1 Oertel, Wolfgang
A1 Janzen, Annette
A1 Plazzi, Giuseppe
A1 Antelmi, Elena
A1 Figorilli, Michela
A1 Puligheddu, Monica
A1 Mollenhauer, Brit
A1 Trenkwalder, Claudia
A1 Sixel-Döring, Friederike
A1 De Cock, Valérie Cochen
A1 Monaca, Christelle Charley
A1 Heidbreder, Anna
A1 Ferini-Strambi, Luigi
A1 Dijkstra, Femke
A1 Viaene, Mineke
A1 Abril, Beatriz
A1 Boeve, Bradley F.
A1 Trempe, Jean-François
A1 Rouleau, Guy A.
A1 Postuma, Ronald B.
A1 Gan-Or, Ziv
YR 2021
UL http://n.neurology.org/content/early/2021/01/04/WNL.0000000000011464.abstract
AB Objective: To examine the role of genes identified through genome-wide association studies (GWASs) of Parkinson disease (PD) in the risk of isolated rapid-eye-movement (REM) sleep behavior disorder (iRBD).Methods: We fully sequenced 25 genes previously identified in GWASs of PD, in a total of 1,039 iRBD patients and 1,852 controls. The role of rare heterozygous variants in these genes was examined using burden tests. The contribution of biallelic variants was further tested. To examine the potential impact 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 &gt;50X and 0.0004 at &gt;30X), mainly driven by three nonsynonymous variants (p.V85M, p.I101V and p.V272M) found in 22 (1.2%) controls vs. two (0.2%) patients. All three variants seem to be loss-of-function variants with a potential effect on the protein structure and stability. Rare non-coding heterozygous variants in LAMP3 were also associated with iRBD (p=0.0006 at &gt;30X). 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 non-coding variants in LAMP3 are associated with iRBD. Additional studies are required to replicate these results and examine whether loss-of-function of BST1 could be a therapeutic target.