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.

Department of Clinical Neuroimmunology University of Munich Germany

Department of Neurology Asklepios Fachklinikum Teupitz Germany

Department of Neurology Carl Thiem Klinikum Cottbus Germany

Department of Neurology Charité Universitätsmedizin Berlin Berlin Germany and German Center for Neurodegenerative Diseases Berlin Berlin Germany

Department of Neurology Charles University Prague Czech Republic

Department of Neurology Christian Albrechts University Kiel Germany

Department of Neurology Klinikum Osnabrück Germany

Department of Neurology Klinikum St Georg Wermsdorf Germany

Department of Neurology Martha Maria Hospital Halle Germany

Department of Neurology Medical Faculty Heinrich Heine University Düsseldorf Germany

Department of Neurology Neuroimmunological Section University Hospital Rostock Germany

Department of Neurology Ulm University Germany

Department of Neurology University Hospital Hannover Germany

Department of Neurology University Hospital Münster Germany

Department of Neurology University of Leipzig Germany

Department of Neurology University of Lübeck Lübeck Germany

Department of Pediatric Neurology Vestische Kinder und Jugendklinik Datteln University Witten Herdecke Germany

Epilepsy Centre Bethel Krankenhaus Mara Bielefeld Germany

Institute of Clinical Molecular Biology Christian Albrechts University of Kiel Germany

Institute of Epidemiology Department of Neurology Neuroimmunological Section Christian Albrechts University Kiel Germany

Institute of Neuroimmunology and Multiple Sclerosis University Medical Center Hamburg Eppendorf Germany

Neuroimmunology section Institute of Clinical Chemistry University Hospital Schleswig Holstein Kiel Lübeck Germany

Citace poskytuje Crossref.org

Genome-wide Association Study Identifies 2 New Loci Associated With Anti-NMDAR Encephalitis