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Müller, Stefanie H.; Färber, Anna; Pruess, Harald; Melzer, Nico; Golombeck, Kristin S.; Kümpfel, Tania; Thaler, Franziska; Elisak, Martin; Lewerenz, Jan; Kaufmann, Max; Suehs, Kurt-Wolfram; Ringelstein, Marius; Kellinghaus, Christoph; Bien, Christian G.; Kraft, Andrea; Zettl, Uwe K.; Ehrlich, Sven; Handreka, Robert; Rostasy, Kevin; Bergh, Florian Then; Faiss, Jürgen H.; Lieb, Wolfgang; Franke, Andre; Kuhlenbäumer, Gregor; Wandinger, Klaus-Peter and Leypoldt, Frank (2018): Genetic predisposition in anti-LGI1 and anti-NMDA receptor encephalitis. In: Annals of Neurology, Vol. 83, No. 4: pp. 863-869

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Abstract

We performed a genome-wide association study in 1,194 controls and 150 patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR, n=96) or anti-leucine-rich glioma-inactivated1 (anti-LGI1, n=54) autoimmune encephalitis. Anti-LGI1 encephalitis was highly associated with 27 single-nucleotide polymorphisms (SNPs) in the HLA-II region (leading SNP rs2858870 p=1.22x10(-17), OR=13.66 [7.50-24.87]). Potential associations, below genome-wide significance, were found with rs72961463 close to the doublecortin-like kinase 2 gene (DCLK2) and rs62110161 in a cluster of zinc-finger genes. HLA allele imputation identified association of anti-LGI1 encephalitis with HLA-II haplotypes encompassing DRB1*07:01, DQA1*02:01 and DQB1*02:02 (p<2.2x10(-16)) and anti-NMDAR encephalitis with HLA-I allele B*07:02 (p=0.039). No shared genetic risk factors between encephalitides were identified. Ann Neurol 2018;83:863-869

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