Genetic predisposition in anti‐LGI1 and anti‐NMDA receptor encephalitis

Authors: Stefanie H. Mueller, Anna Färber, Harald Prüß, Nico Melzer, Kristin S. Golombeck, Tania Kümpfel, Franziska Thaler, Martin Elišák, Jan Lewerenz, Max Kaufmann, Kurt‐Wolfram Sühs, Marius Ringelstein, Christoph Kellinghaus, Christian G. Bien, Andrea Kraft, Uwe K. Zettl, Sven Ehrlich, Robert Handreka, Kevin Rostásy, Florian Then Bergh, Jürgen Faiss, Wolfgang Lieb, Andre Franke, Gregor Kuhlenbäumer, Klaus‐Peter Wandinger, Frank Leypoldt - Annals of Neurology 2018 cited by 155

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 = 1.22 × 10 −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 < 2.2 × 10 −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