Circulating proteins play key roles 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, of which 50 were novel. Integration of pQTL data with eQTL and disease GWAS provided insights into pathogenesis, implicating lymphotoxin-alpha (LTA) in multiple sclerosis. Using Mendelian randomisation (MR), we identified both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant causal roles for CD40 in rheumatoid arthritis, multiple sclerosis and inflammatory bowel disease. Our results highlight novel potential therapeutic avenues, including CXCL5 in ulcerative colitis (UC), a finding supported by elevated gut CXCL5 expression in UC patients. Our data provide a powerful resource to facilitate future drug target prioritization.