Tietz, Anja K. and Angstwurm, Klemens and Baumgartner, Tobias and Doppler, Kathrin and Eisenhut, Katharina and Elisak, Martin and Franke, Andre and Golombeck, Kristin S. and Handreka, Robert and Kaufmann, Max and Kraemer, Markus and Kraft, Andrea and Lewerenz, Jan and Lieb, Wolfgang and Madlener, Marie and Melzer, Nico and Mojzisova, Hana and Moeller, Peter and Pfefferkorn, Thomas and Pruess, Harald and Rostasy, Kevin and Schnegelsberg, Margret and Schroeder, Ina and Siebenbrodt, Kai and Suehs, Kurt-Wolfram and Wickel, Jonathan and Wandinger, Klaus-Peter and Leypoldt, Frank and Kuhlenbaeumer, Gregor (2021) Genome-wide Association Study Identifies 2 New Loci Associated With Anti-NMDAR Encephalitis. NEUROLOGY-NEUROIMMUNOLOGY & NEUROINFLAMMATION, 8 (6): e1085. ISSN 2332-7812,
Full text not available from this repository. (Request a copy)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: | Article |
|---|---|
| Uncontrolled Keywords: | LIVER-X RECEPTOR; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Neurologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 14:12 |
| Last Modified: | 27 Sep 2022 14:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/48117 |
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