TY - UNPB
T1 - Altered IL-6 signalling and risk of tuberculosis disease
T2 - a meta-analysis and Mendelian randomisation study
AU - International Host TB Genetics Consortium
AU - Hamilton, Fergus
AU - Schurz, Haiko
AU - Yates, Tom A
AU - Gilchrist, James J
AU - Möller, Marlo
AU - Naranbhai, Vivek
AU - Ghazal, Peter
AU - Timpson, Nicholas J
AU - Parks, Tom
AU - Pollara, Gabriele
PY - 2023/2/8
Y1 - 2023/2/8
N2 - IL-6 responses are ubiquitous in
Mycobacterium tuberculosis (Mtb) infections, but their role in determining human tuberculosis (TB) disease risk is unknown. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor
(IL6R) gene, focusing on the non-synonymous variant, rs2228145, associated with reduced classical IL-6 signalling, to assess the effect of altered IL-6 activity on TB disease risk. We identified 16 genome wide association studies (GWAS) of TB disease collating 17,982 cases of TB disease and 972,389 controls across 4 continents. Meta-analyses and Mendelian randomisation analyses revealed that reduced classical IL-6 signalling was associated with lower odds of TB disease, a finding replicated using multiple, independent SNP instruments and 2 separate exposure variables. Our findings establish a causal relationship between IL-6 signalling and the outcome of
Mtb infection, suggesting IL-6 antagonists do not increase the risk of TB disease and should be investigated as adjuncts in treatment.
AB - IL-6 responses are ubiquitous in
Mycobacterium tuberculosis (Mtb) infections, but their role in determining human tuberculosis (TB) disease risk is unknown. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor
(IL6R) gene, focusing on the non-synonymous variant, rs2228145, associated with reduced classical IL-6 signalling, to assess the effect of altered IL-6 activity on TB disease risk. We identified 16 genome wide association studies (GWAS) of TB disease collating 17,982 cases of TB disease and 972,389 controls across 4 continents. Meta-analyses and Mendelian randomisation analyses revealed that reduced classical IL-6 signalling was associated with lower odds of TB disease, a finding replicated using multiple, independent SNP instruments and 2 separate exposure variables. Our findings establish a causal relationship between IL-6 signalling and the outcome of
Mtb infection, suggesting IL-6 antagonists do not increase the risk of TB disease and should be investigated as adjuncts in treatment.
U2 - 10.1101/2023.02.07.23285472
DO - 10.1101/2023.02.07.23285472
M3 - Preprint
C2 - 36798349
T3 - medRxiv
BT - Altered IL-6 signalling and risk of tuberculosis disease
ER -
