Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis

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 (<i>p</i> < 1 × 10<sup>-5</sup>) intronic and exonic variants in <i>ABCG1</i>, the only gene significantly associated with TBE susceptibility. These variants were shown to influence <i>ABCG1</i> expression in peripheral blood, a finding corroborated by RNA expression analysis. <i>In vitro</i> inhibition or silencing of <i>ABCG1</i> significantly reduced TBEV replication in both neuronal cells and macrophages, highlighting the potential role of <i>ABCG1</i> in TBEV biology. Additionally, we detected a genome-wide significant variant within <i>TEX41</i>, located downstream of <i>ZEB1</i>, associated with severe forms of TBE. These findings provide novel insights into the genetic factors underlying TBE susceptibility and severity.

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Journal
iScience
Published
2025-11-14
DOI
https://doi.org/10.1016/j.isci.2025.114017
Primary Topic
Vector-borne infectious diseases
Type
article
Field-Weighted Citation Impact
0.00

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article

Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis

Alexander Binder, Christoph Haudum, Martin L. Hibberd, Joanna Zajkowska et al.
iScience
Vector-borne infectious diseases
article

Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis

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

Abstract

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 (<i>p</i> < 1 × 10<sup>-5</sup>) intronic and exonic variants in <i>ABCG1</i>, the only gene significantly associated with TBE susceptibility. These variants were shown to influence <i>ABCG1</i> expression in peripheral blood, a finding corroborated by RNA expression analysis. <i>In vitro</i> inhibition or silencing of <i>ABCG1</i> significantly reduced TBEV replication in both neuronal cells and macrophages, highlighting the potential role of <i>ABCG1</i> in TBEV biology. Additionally, we detected a genome-wide significant variant within <i>TEX41</i>, located downstream of <i>ZEB1</i>, associated with severe forms of TBE. These findings provide novel insights into the genetic factors underlying TBE susceptibility and severity.

iScienceVol. 28(12)
Lithuanian University of Health Sciences (LT), University of Bonn (DE), Medical University of Białystok (PL), University of Liverpool (GB), Medical University of Graz (AT), Charles University (CZ), Masaryk University (CZ), Age UK (GB), Ljubljana University Medical Centre (SI), Royal Liverpool University Hospital (GB), London School of Hygiene & Tropical Medicine (GB), University Hospital Brno (CZ), Children's Clinical University Hospital (LV), Veterinary Research Institute (CZ), Nemocnice České Budějovice (CZ), Institute of Parasitology (CZ), Czech Academy of Sciences, Biology Centre (CZ), University of Tartu (EE), Medical University of Vienna (AT)
Pfizer, European Commission, Grantová Agentura České Republiky, Karl-Franzens-Universität Graz, Amt der Steiermärkischen Landesregierung, Medizinische Universität Graz, Lietuvos Sveikatos Mokslų Universitetas, NIH Clinical Center
Openalex Percentile: Top 64%
Vector-borne infectious diseases
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