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Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets

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dc.contributor.authorZhao, J.H.
dc.contributor.authorStacey, D.
dc.contributor.authorEriksson, N.
dc.contributor.authorMacdonald Dunlop, E.
dc.contributor.authorPeters, J.E.
dc.date.issued2023
dc.descriptionData source: Supplementary information, https://doi.org/10.1038/s41590-023-01588-w Link to a related website: https://doi.org/10.1038/s41590-023-01635-6, Author correction
dc.description.abstractCirculating proteins have important functions in inflammation and a broad range of diseases. To identify genetic influences on inflammation-related proteins, we conducted a genome-wide protein quantitative trait locus (pQTL) study of 91 plasma proteins measured using the Olink Target platform in 14,824 participants. We identified 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease genome-wide association studies provided insight into pathogenesis, implicating lymphotoxin-α in multiple sclerosis. Using Mendelian randomization (MR) to assess causality in disease etiology, we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant effects of CD40 on risk of rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicated CXCL5 in the etiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in patients with UC. These results identify targets of existing drugs and provide a powerful resource to facilitate future drug target prioritization.
dc.identifier.citationNature Immunology, 2023; 24(9):1450-1551
dc.identifier.doi10.1038/s41590-023-01588-w
dc.identifier.issn1529-2908
dc.identifier.issn1529-2916
dc.identifier.urihttps://hdl.handle.net/11541.2/35313
dc.language.isoen
dc.publisherNature Publishing Group
dc.rightsCopyright 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. (http://creativecommons.org/licenses/by/4.0/)
dc.source.urihttps://doi.org/10.1038/s41590-023-01588-w
dc.subjectinflammatory proteins
dc.subjecttherapeutic targets
dc.subjectdisease risk
dc.titleGenetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12275847500001831 13275847490001831 Open Access Published Version
ror.mmsid9916791729801831

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