Tietz, Anja K., Angstwurm, Klemens, Baumgartner, Tobias, Doppler, Kathrin ORCID: 0000-0003-2883-0009, Eisenhut, Katharina ORCID: 0000-0001-6448-3126, Elisak, Martin, Franke, Andre ORCID: 0000-0003-1530-5811, Golombeck, Kristin S., Handreka, Robert, Kaufmann, Max ORCID: 0000-0002-1954-4425, Kraemer, Markus, Kraft, Andrea, Lewerenz, Jan, Lieb, Wolfgang, Madlener, Marie, Melzer, Nico, Mojzisova, Hana, Moeller, Peter, Pfefferkorn, Thomas, Pruess, Harald, Rostasy, Kevin, Schnegelsberg, Margret, Schroeder, Ina, Siebenbrodt, Kai, Suehs, Kurt-Wolfram, Wickel, Jonathan, Wandinger, Klaus-Peter, Leypoldt, Frank ORCID: 0000-0002-8972-515X and Kuhlenbaeumer, Gregor (2021). Genome-wide Association Study Identifies 2 New Loci Associated With Anti-NMDAR Encephalitis. Neurol.-Neuroimmunol. Neuroinflammation, 8 (6). PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 2332-7812

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tietz, Anja K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Angstwurm, KlemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baumgartner, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doppler, KathrinUNSPECIFIEDorcid.org/0000-0003-2883-0009UNSPECIFIED
Eisenhut, KatharinaUNSPECIFIEDorcid.org/0000-0001-6448-3126UNSPECIFIED
Elisak, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, AndreUNSPECIFIEDorcid.org/0000-0003-1530-5811UNSPECIFIED
Golombeck, Kristin S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Handreka, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaufmann, MaxUNSPECIFIEDorcid.org/0000-0002-1954-4425UNSPECIFIED
Kraemer, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kraft, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lewerenz, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lieb, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Madlener, MarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Melzer, NicoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mojzisova, HanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Moeller, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfefferkorn, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pruess, HaraldUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rostasy, KevinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schnegelsberg, MargretUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeder, InaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Siebenbrodt, KaiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Suehs, Kurt-WolframUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wickel, JonathanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wandinger, Klaus-PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Leypoldt, FrankUNSPECIFIEDorcid.org/0000-0002-8972-515XUNSPECIFIED
Kuhlenbaeumer, GregorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-606471
DOI: 10.1212/NXI.0000000000001085
Journal or Publication Title: Neurol.-Neuroimmunol. Neuroinflammation
Volume: 8
Number: 6
Date: 2021
Publisher: LIPPINCOTT WILLIAMS & WILKINS
Place of Publication: PHILADELPHIA
ISSN: 2332-7812
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
LIVER-X RECEPTORMultiple languages
Clinical Neurology; NeurosciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/60647

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