Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle

John F.  O’Grady; Gillian P.  McHugo; James A.  Ward; Thomas J.  Hall; Sarah L.  Faherty O’Donnell; Carolina N.  Correia; John A.  Browne; Michael McDonald; Eamonn  Gormley; Valentina Riggio; James Prendergast; Emily Clark; Hubert  Pausch; Kieran G Meade; Isobel Claire Gormley; Stephen V. Gordon; David E MacHugh

doi:10.1038/s42003-025-07846-x

Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle

John F. O’Grady, Gillian P. McHugo, James A. Ward, Thomas J. Hall, Sarah L. Faherty O’Donnell, Carolina N. Correia, John A. Browne, Michael McDonald, Eamonn Gormley, Valentina Riggio, James Prendergast, Emily Clark, Hubert Pausch, Kieran G Meade, Isobel Claire Gormley, Stephen V. Gordon, David E MacHugh

Royal (Dick) School of Veterinary Studies

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

Abstract

Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis-infected animals and detect 2592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 115 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.

Original language	English
Article number	479
Pages (from-to)	1-18
Number of pages	18
Journal	Communications Biology
Volume	8
Issue number	1
Early online date	24 Mar 2025
DOIs	https://doi.org/10.1038/s42003-025-07846-x
Publication status	Published - 24 Mar 2025

Keywords / Materials (for Non-textual outputs)

Animals
Cattle
Genetic Predisposition to Disease
Genome-Wide Association Study
Genomics
Immunogenetics
Mycobacterium bovis/immunology
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Transcriptome
Tuberculosis, Bovine/genetics

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10.1038/s42003-025-07846-xLicence: Other

s42003-025-07846-xFinal published version, 3.34 MBLicence: Creative Commons: Attribution (CC-BY)

ISP 2 2023/28 Prevention & Control of Infectious Diseases
Wilson, A. (Principal Investigator)
1/04/23 → 31/03/28
Project: Research

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O’Grady, J. F., McHugo, G. P., Ward, J. A., Hall, T. J., Faherty O’Donnell, S. L., Correia, C. N., Browne, J. A., McDonald, M., Gormley, E., Riggio, V., Prendergast, J., Clark, E., Pausch, H., Meade, K. G., Gormley, I. C., Gordon, S. V., & MacHugh, D. E. (2025). Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle. Communications Biology, 8(1), 1-18. Article 479. https://doi.org/10.1038/s42003-025-07846-x

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title = "Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle",

abstract = "Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis-infected animals and detect 2592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 115 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.",

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author = "O{\textquoteright}Grady, {John F.} and McHugo, {Gillian P.} and Ward, {James A.} and Hall, {Thomas J.} and {Faherty O{\textquoteright}Donnell}, {Sarah L.} and Correia, {Carolina N.} and Browne, {John A.} and Michael McDonald and Eamonn Gormley and Valentina Riggio and James Prendergast and Emily Clark and Hubert Pausch and Meade, {Kieran G} and Gormley, {Isobel Claire} and Gordon, {Stephen V.} and MacHugh, {David E}",

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doi = "10.1038/s42003-025-07846-x",

language = "English",

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O’Grady, JF, McHugo, GP, Ward, JA, Hall, TJ, Faherty O’Donnell, SL, Correia, CN, Browne, JA, McDonald, M, Gormley, E, Riggio, V , Prendergast, J, Clark, E, Pausch, H, Meade, KG, Gormley, IC, Gordon, SV & MacHugh, DE 2025, 'Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle', Communications Biology, vol. 8, no. 1, 479, pp. 1-18. https://doi.org/10.1038/s42003-025-07846-x

TY - JOUR

T1 - Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle

AU - O’Grady, John F.

AU - McHugo, Gillian P.

AU - Ward, James A.

AU - Hall, Thomas J.

AU - Faherty O’Donnell, Sarah L.

AU - Correia, Carolina N.

AU - Browne, John A.

AU - McDonald, Michael

AU - Gormley, Eamonn

AU - Riggio, Valentina

AU - Prendergast, James

AU - Clark, Emily

AU - Pausch, Hubert

AU - Meade, Kieran G

AU - Gormley, Isobel Claire

AU - Gordon, Stephen V.

AU - MacHugh, David E

PY - 2025/3/24

Y1 - 2025/3/24

N2 - Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis-infected animals and detect 2592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 115 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.

AB - Mycobacterium bovis causes bovine tuberculosis (bTB), an infectious disease of cattle that represents a zoonotic threat to humans. Research has shown that the peripheral blood (PB) transcriptome is perturbed during bTB disease but the genomic architecture underpinning this transcriptional response remains poorly understood. Here, we analyse PB transcriptomics data from 63 control and 60 confirmed M. bovis-infected animals and detect 2592 differently expressed genes perturbing multiple immune response pathways. Leveraging imputed genome-wide SNP data, we characterise thousands of cis-expression quantitative trait loci (eQTLs) and show that the PB transcriptome is substantially impacted by intrapopulation genomic variation during M. bovis infection. Integrating our cis-eQTL data with bTB susceptibility GWAS summary statistics, we perform a transcriptome-wide association study and identify 115 functionally relevant genes (including RGS10, GBP4, TREML2, and RELT) and provide important new omics data for understanding the host response to mycobacterial infections that cause tuberculosis in mammals.

KW - Animals

KW - Cattle

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genomics

KW - Immunogenetics

KW - Mycobacterium bovis/immunology

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci

KW - Transcriptome

KW - Tuberculosis, Bovine/genetics

U2 - 10.1038/s42003-025-07846-x

DO - 10.1038/s42003-025-07846-x

M3 - Article

C2 - 40128580

SN - 2399-3642

VL - 8

SP - 1

EP - 18

JO - Communications Biology

JF - Communications Biology

IS - 1

M1 - 479

ER -

Integrative genomics sheds light on the immunogenetics of tuberculosis in cattle

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

ISP 2 2023/28 Prevention & Control of Infectious Diseases

Cite this