Altered IL-6 signalling and risk of tuberculosis: a multi-ancestry mendelian randomisation study

Fergus Hamilton, Haiko Schurz, Tom Yates, James J. Gilchrist, Marlo Möller, Vivek Naranbhai, Peter Ghazal, Nicholas J. Timpson, Shaheen Akhtar, Mohammad Anwar, Omar Asgar, Samina Ashraf, Saeed Bidi, Gerome Breen, James Broster, Raymond Chung, David Collier, Charles J Curtis, Shabana Chaudhary, Grainne Colligan, Panos Deloukas, Ceri Durham, Faiza Durrani, Fabiola Eto, Sarah Finer, Joseph Gafton, Ana Angel, Chris Griffiths, Joanne Harvey, Teng Heng, Sam Hodgson, Qin Qin Huang, Matt Hurles, Karen A Hunt, Shapna Hussain, Kamrul Islam, Vivek Iyer, Benjamin M Jacobs, Georgios Kalantzis, Ahsan Khan, Claudia Langenberg, Cath Lavery, Sang Hyuck Lee, Daniel MacArthur, Sidra Malik, Daniel Malawsky, Hilary Martin, Dan Mason, Rohini Mathur, Mohammed Bodrul Mazid, John McDermott, Caroline Morton, Bill Newman, Elizabeth Owor, Asma Qureshi, Shwetha Ramachandrappa, Mehru Raza, Jessry Russell, Nishat Safa, Miriam Samuel, Moneeza Siddiqui, Michael Simpson, John Solly, Marie Spreckley, Daniel Stow, Michael Taylor, Richard C Trembath, Karen Tricker, David A van Heel, Klaudia Walter, Caroline Winckley, Suzanne Wood, John Wright, Ishevanhu Zengeya, Julia Zöllner, Haiko Schurz, Vivek Naranbhai, Tom A Yates, James J Gilchrist, Tom Parks, Peter J Dodd, Marlo Möller, Eileen G Hoal, Andrew P Morris, Adrian V S Hill, Reinout van Crevel, Arjan van Laarhoven, Tom H M Ottenhoff, Andres Metspalu, Reedik Magi, Christian G Meyer, Magda Ellis, Thorsten Thye, Surakameth Mahasirimongkol, Ekawat Pasomsub, Katsushi Tokunaga, Yosuke Omae, Hideki Yanai, Taisei Mushiroda, Michiaki Kubo

The Lancet Microbe · 2024

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Summary

BACKGROUND: The role of IL-6 responses in human tuberculosis risk is unknown. IL-6 signalling inhibitors, such as tocilizumab, are thought to increase the risk of progression to tuberculosis, and screening for latent Mycobacterium tuberculosis infection before using these drugs is widely recommended. We used single nucleotide polymorphisms (SNPs) in and near the IL-6 receptor gene (IL6R), including the non-synonymous variant, rs2228145, for which the C allele contributes to reduced classic (cis) IL-6 signalling activity, to test the hypothesis that altered IL-6 signalling is causally associated with the risk of developing tuberculosis. METHODS: We performed a meta-analysis of genome-wide association studies (GWAS) published in English from database inception to Jan 1, 2024. GWAS were ident

Source type: Peer-reviewed study
DOI: 10.1016/s2666-5247(24)00162-9
Catalogue ID: SNmoj7nr4w-eeh6s2

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