Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10431710" target="_blank" >RIV/00216208:11110/21:10431710 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/21:10431710
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=GjuoUwVxZL" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=GjuoUwVxZL</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1212/WNL.0000000000011464" target="_blank" >10.1212/WNL.0000000000011464</a>
Alternative languages
Result language
angličtina
Original language name
Novel Associations of BST1 and LAMP3 With REM Sleep Behavior Disorder
Original language description
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 >50x and 0.0004 at >30x), 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 >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 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Neurology
ISSN
0028-3878
e-ISSN
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Volume of the periodical
96
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
"e1402"-"e1412"
UT code for WoS article
000656632700014
EID of the result in the Scopus database
2-s2.0-85102725092