Pulse Brain · Growing Health Evidence Index
Peer-reviewed

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

Jing Hua Zhao, David Stacey, Niclas Eriksson, Erin Macdonald-Dunlop, Åsa K. Hedman, Anette Kalnapenkis, Stefan Enroth, Domenico Cozzetto, Jonathan Digby‐Bell, Jonathan Marten, Lasse Folkersen, Christian Herder, Lina Jönsson, Sarah E. Bergen, Christian Gieger, Elise J. Needham, Praveen Surendran, Andres Metspalu, Lili Milani, Reedik Mägi, Mari Nelis, Georgi Hudjašov, Dirk S. Paul, Ozren Polašek, Barbara Thorand, Harald Grallert, Michael Roden, Urmo Võsa, Tõnu Esko, Caroline Hayward, Åsa Johansson, Ulf Gyllensten, Nick Powell, Oskar Hansson, Niklas Mattsson, Peter K. Joshi, John Danesh, Leonid Padyukov, Lars Klareskog, Mikael Landén, James F. Wilson, Agneta Siegbahn, Lars Wallentin, Anders Mälarstig, Adam S. Butterworth, James E. Peters

Nature Immunology · 2023

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Summary

Circulating 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 multip

Source type
Peer-reviewed study
DOI
10.1038/s41590-023-01588-w
Catalogue ID
SNmohdw6s2-vx0ezu
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