Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets
Publication: Nature Immunology
Jing Hua Zhao, David Stacey, Niclas Eriksson, Erin Macdonald-Dunlop, Asa K Hedman et al
18 July 2023
Aberrant inflammatory responses play a role in pathogenesis of many diseases, including autoimmune conditions, cardiovascular diseases and cancers. In this study of genetic influences on inflammation-related proteins, an international team conducted a genome-wide association study of 91 plasma proteins in ~15,000 participants within the SCALLOP Consortium.
Having identified 180 gene-protein associations, they integrated with gene expression and disease genetics to provide insights into disease aetiology, implicating FGF5 in hypertension and cardiovascular disease, and lymphotoxin-α in multiple sclerosis.
The team identified both shared and distinct effects of specific proteins across immune mediated diseases, including directionally discordant functions for CD40 in rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease, and a role for CXCL5 in the aetiology of ulcerative colitis UC but not Crohns disease.
These results provide a powerful resource to understand the role of chronic inflammation in a wide range of diseases and facilitate future drug target prioritisation.
