Genome-wide Association Study Identifies 2 New Loci Associated With Anti-NMDAR Encephalitis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F21%3A10432319" target="_blank" >RIV/00064203:_____/21:10432319 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/21:10432319
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=CvRG5sVsVp" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=CvRG5sVsVp</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1212/NXI.0000000000001085" target="_blank" >10.1212/NXI.0000000000001085</a>
Alternative languages
Result language
angličtina
Original language name
Genome-wide Association Study Identifies 2 New Loci Associated With Anti-NMDAR Encephalitis
Original language description
BACKGROUND AND OBJECTIVES: To investigate the genetic determinants of the most common type of antibody-mediated autoimmune encephalitis, anti-NMDA receptor (anti-NMDAR) encephalitis. METHODS: We performed a genome-wide association study in 178 patients with anti-NMDAR encephalitis and 590 healthy controls, followed by a colocalization analysis to identify putatively causal genes. RESULTS: We identified 2 independent risk loci harboring genome-wide significant variants (p < 5 x 10(-8), OR >= 2.2), 1 on chromosome 15, harboring only the LRRK1 gene, and 1 on chromosome 11 centered on the ACP2 and NR1H3 genes in a larger region of high linkage disequilibrium. Colocalization signals with expression quantitative trait loci for different brain regions and immune cell types suggested ACP2, NR1H3, MADD, DDB2, and C11orf49 as putatively causal genes. The best candidate genes in each region are LRRK1, encoding leucine-rich repeat kinase 1, a protein involved in B-cell development, and NR1H3 liver X receptor alpha, a transcription factor whose activation inhibits inflammatory processes. DISCUSSION: This study provides evidence for relevant genetic determinants of antibody-mediated autoimmune encephalitides outside the human leukocyte antigen (HLA) region. The results suggest that future studies with larger sample sizes will successfully identify additional genetic determinants and contribute to the elucidation of the pathomechanism.
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: Neuroimmunology & Neuroinflammation
ISSN
2332-7812
e-ISSN
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Volume of the periodical
8
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
11
Pages from-to
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UT code for WoS article
000712132000031
EID of the result in the Scopus database
2-s2.0-85117338493