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Genome-wide association study identifies as a susceptibility locus for tick-borne encephalitis.

iScience

Authors: Piyush G Gampawar, Manfred G Sagmeister, Daniel Růžek, Nina A Schweintzger, Edith Hofer, Benno Kohlmaier, Vendula Švendová, Petra Bogovič, Joanna M Zajkowska, Lenka Krbková, Věra Štruncová, Auksė Mickienė, Daniela S Kohlfürst, Astrid Sonnleitner, Andrea Fořtová, Michaela Berankova, Martina Pychova, Dace Zavadska, Neneh Sallah, Alexander Pichler, Dalibor Sedláček, Aleš Chrdle, Christoph Haudum, Barbara Obermayer-Pietsch, Per Hoffmann, Markus M Nöthen, Mari-Liis Tammesoo, Andres Metspalu, Petr Husa, Karin Stiasny, Alexander Binder, Andrea Berghold, Franc Strle, Martin L Hibberd, Werner Zenz

Tick-borne encephalitis (TBE) is a viral infection of the central nervous system, caused by the tick-borne encephalitis virus (TBEV) presenting clinically as meningitis, meningoencephalitis, and meningoencephalomyelitis. To investigate genetic susceptibility to TBE, and its severe forms, we conducted a genome-wide association study in the European population comprising 1,600 TBE cases and 9,699 controls. We identified several suggestive ( < 1 × 10) intronic and exonic variants in , the only gene significantly associated with TBE susceptibility. These variants were shown to influence expression in peripheral blood, a finding corroborated by RNA expression analysis. inhibition or silencing of significantly reduced TBEV replication in both neuronal cells and macrophages, highlighting the potential role of in TBEV biology. Additionally, we detected a genome-wide significant variant within , located downstream of , associated with severe forms of TBE. These findings provide novel insights into the genetic factors underlying TBE susceptibility and severity.

© 2025 The Authors.

PMID: 41377660

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