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More than 90% of patients carry the human leukocyte antigen (HLA) class II allele, HLA-DRB1*07:01. However, this is also present in 25% of healthy controls. Therefore, we hypothesized the presence of additional genetic predispositions.<\/jats:p>\n                  <jats:p>In this genome-wide association study and meta-analysis, we studied a discovery cohort of 131 French LGI1-Ab-E and a validation cohort of 126 American, British and Irish LGI1-Ab-E patients, ancestry-matched to 2613 and 2538 European controls, respectively.<\/jats:p>\n                  <jats:p>Outside the known major HLA signal, we found two single nucleotide polymorphisms at genome-wide significance (P &amp;lt; 5 \u00d7 10\u22128), implicating PTPRD, a protein tyrosine phosphatase, and LINC00670, a non-protein coding RNA gene. Meta-analysis defined four additional non-HLA loci, including the protein coding COBL gene. Polygenic risk scores with and without HLA variants proposed a contribution of non-HLA loci. In silico network analyses suggested LGI1 and PTPRD-mediated interactions via the established receptors of LGI1, ADAM22 and ADAM23.<\/jats:p>\n                  <jats:p>Our results identify new genetic loci in LGI1-Ab-E. These findings present opportunities for mechanistic studies and offer potential markers of susceptibility, prognostics and therapeutic responses.<\/jats:p>","DOI":"10.1093\/brain\/awae349","type":"journal-article","created":{"date-parts":[[2024,10,24]],"date-time":"2024-10-24T15:24:06Z","timestamp":1729783446000},"page":"737-745","source":"Crossref","is-referenced-by-count":14,"title":["Novel risk loci in LGI1-antibody encephalitis: genome-wide association study discovery and validation cohorts"],"prefix":"10.1093","volume":"148","author":[{"given":"Sophie N M","family":"Binks","sequence":"first","affiliation":[{"name":"Oxford Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU ,","place":["UK"]},{"name":"Department of Neurology, John Radcliffe Hospital , Oxford OX3 9DU ,","place":["UK"]},{"name":"Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford , Oxford OX3 7BN 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,","place":["Ireland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T\u00e2nia","family":"Kawasaki de Araujo","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Genomic Medicine, School of Medical Sciences, University of Campinas - UNICAMP, Campinas CEP 13083-888 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R","family":"Harper","sequence":"additional","affiliation":[{"name":"Clinical Development, Research and Early Development, Respiratory and Immunology (R&I), BioPharmaceuticals R&D, AstraZeneca , Cambridge CB2 0AA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C","family":"Brown","sequence":"additional","affiliation":[{"name":"Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford , Oxford OX3 7BN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda 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CB10 1SA ,","place":["UK"]},{"name":"Institute of Translational Genomics, Helmholtz Zentrum M\u00fcnchen, German Research Center for Environmental Health , D-85764 Neuherberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4502-2209","authenticated-orcid":false,"given":"Alexander J","family":"Mentzer","sequence":"additional","affiliation":[{"name":"Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford , Oxford OX3 7BN ,","place":["UK"]},{"name":"Nuffield Department of Medicine, University of Oxford , Oxford, OX3 7BN ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman","family":"Delanty","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland , Dublin, Dublin 2 ,","place":["Ireland"]},{"name":"FutureNeuro SFI Research Centre, Royal College of Surgeons in Ireland , Dublin, Dublin 2 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