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

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

doi:10.1016/j.isci.2025.114017

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

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 (Corresponding Author)

Rīga Stradiņš University

Research output: Contribution to journal › Article › peer-review

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

Original language	English
Article number	114017
Journal	iScience
Volume	28
Issue number	12
DOIs	https://doi.org/10.1016/j.isci.2025.114017
Publication status	Published - 19 Dec 2025

Field of Science*

3.2 Clinical medicine

Publication Type*

1.1. Scientific article indexed in Web of Science and/or Scopus database

Access to Document

10.1016/j.isci.2025.114017Licence: CC BY

Genome-wide association studyFinal published version, 4.92 MBLicence: CC BY

https://linkinghub.elsevier.com/retrieve/pii/S2589004225022783

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Gampawar, P. G., Sagmeister, M. G., Růžek, D., Schweintzger, N. A., Hofer, E., Kohlmaier, B., Švendová, V., Bogovič, P., Zajkowska, J. M., Krbková, L., Štruncová, V., Mickienė, A., Kohlfürst, D. S., Sonnleitner, A., Fořtová, A., Berankova, M., Pychova, M., Zavadska, D., Sallah, N., ... Zenz, W. (2025). Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis. iScience, 28(12), Article 114017. https://doi.org/10.1016/j.isci.2025.114017

@article{d5489e8b90214fcb8afbb79b3588dfbe,

title = "Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis",

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

author = "Gampawar, \{Piyush G.\} and Sagmeister, \{Manfred G.\} and Daniel Rů{\v z}ek and Schweintzger, \{Nina A.\} and Edith Hofer and Benno Kohlmaier and Vendula {\v S}vendov{\'a} and Petra Bogovi{\v c} and Zajkowska, \{Joanna M.\} and Lenka Krbkov{\'a} and V{\v e}ra {\v S}truncov{\'a} and Auksė Mickienė and Kohlf{\"u}rst, \{Daniela S.\} and Astrid Sonnleitner and Andrea Fo{\v r}tov{\'a} and Michaela Berankova and Martina Pychova and Dace Zavadska and Neneh Sallah and Alexander Pichler and Dalibor Sedl{\'a}{\v c}ek and Ale{\v s} Chrdle and Christoph Haudum and Barbara Obermayer-Pietsch and Per Hoffmann and N{\"o}then, \{Markus M.\} and Mari-Liis Tammesoo and Andres Metspalu and Petr Husa and Karin Stiasny and Alexander Binder and Andrea Berghold and Franc Strle and Hibberd, \{Martin L.\} and Werner Zenz",

note = "Publisher Copyright: {\textcopyright} 2025 The Authors",

year = "2025",

month = dec,

day = "19",

doi = "10.1016/j.isci.2025.114017",

language = "English",

volume = "28",

journal = "iScience",

issn = "2589-0042",

publisher = "Elsevier Inc.",

number = "12",

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Gampawar, PG, Sagmeister, MG, Růžek, D, Schweintzger, NA, Hofer, E, Kohlmaier, B, Švendová, V, Bogovič, P, Zajkowska, JM, Krbková, L, Štruncová, V, Mickienė, A, Kohlfürst, DS, Sonnleitner, A, Fořtová, A, Berankova, M, Pychova, M, Zavadska, D, Sallah, N, Pichler, A, Sedláček, D, Chrdle, A, Haudum, C, Obermayer-Pietsch, B, Hoffmann, P, Nöthen, MM, Tammesoo, M-L, Metspalu, A, Husa, P, Stiasny, K, Binder, A, Berghold, A, Strle, F, Hibberd, ML & Zenz, W 2025, 'Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis', iScience, vol. 28, no. 12, 114017. https://doi.org/10.1016/j.isci.2025.114017

TY - JOUR

T1 - Genome-wide association study identifies ABCG1 as a susceptibility locus for tick-borne encephalitis

AU - Gampawar, Piyush G.

AU - Sagmeister, Manfred G.

AU - Růžek, Daniel

AU - Schweintzger, Nina A.

AU - Hofer, Edith

AU - Kohlmaier, Benno

AU - Švendová, Vendula

AU - Bogovič, Petra

AU - Zajkowska, Joanna M.

AU - Krbková, Lenka

AU - Štruncová, Věra

AU - Mickienė, Auksė

AU - Kohlfürst, Daniela S.

AU - Sonnleitner, Astrid

AU - Fořtová, Andrea

AU - Berankova, Michaela

AU - Pychova, Martina

AU - Zavadska, Dace

AU - Sallah, Neneh

AU - Pichler, Alexander

AU - Sedláček, Dalibor

AU - Chrdle, Aleš

AU - Haudum, Christoph

AU - Obermayer-Pietsch, Barbara

AU - Hoffmann, Per

AU - Nöthen, Markus M.

AU - Tammesoo, Mari-Liis

AU - Metspalu, Andres

AU - Husa, Petr

AU - Stiasny, Karin

AU - Binder, Alexander

AU - Berghold, Andrea

AU - Strle, Franc

AU - Hibberd, Martin L.

AU - Zenz, Werner

PY - 2025/12/19

Y1 - 2025/12/19

N2 - 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 (p < 1 × 10 −5) intronic and exonic variants in ABCG1, the only gene significantly associated with TBE susceptibility. These variants were shown to influence ABCG1 expression in peripheral blood, a finding corroborated by RNA expression analysis. In vitro inhibition or silencing of ABCG1 significantly reduced TBEV replication in both neuronal cells and macrophages, highlighting the potential role of ABCG1 in TBEV biology. Additionally, we detected a genome-wide significant variant within TEX41, located downstream of ZEB1, associated with severe forms of TBE. These findings provide novel insights into the genetic factors underlying TBE susceptibility and severity.

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

UR - https://www.scopus.com/pages/publications/105022465615

U2 - 10.1016/j.isci.2025.114017

DO - 10.1016/j.isci.2025.114017

M3 - Article

SN - 2589-0042

VL - 28

JO - iScience

JF - iScience

IS - 12

M1 - 114017

ER -

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

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