Premium
Genetic predisposition in anti‐LGI1 and anti‐NMDA receptor encephalitis
Author(s) -
Mueller Stefanie H.,
Färber Anna,
Prüss Harald,
Melzer Nico,
Golombeck Kristin S.,
Kümpfel Tania,
Thaler Franziska,
Elisak Martin,
Lewerenz Jan,
Kaufmann Max,
Sühs KurtWolfram,
Ringelstein Marius,
Kellinghaus Christoph,
Bien Christian G.,
Kraft Andrea,
Zettl Uwe K.,
Ehrlich Sven,
Handreka Robert,
Rostásy Kevin,
Then Bergh Florian,
Faiss Jürgen H.,
Lieb Wolfgang,
Franke Andre,
Kuhlenbäumer Gregor,
Wandinger KlausPeter,
Leypoldt Frank
Publication year - 2018
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25216
Subject(s) - single nucleotide polymorphism , encephalitis , autoimmune encephalitis , haplotype , genome wide association study , biology , genetics , snp , allele , anti nmda receptor encephalitis , genetic predisposition , genetic association , gene , genotype , virus
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