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. Here, we identify 180 pQTLs (59 cis, 121 trans). Integration of pQTL data with eQTL and disease GWAS provided insights into pathogenesis, implicating lymphotoxin-alpha in multiple sclerosis. Using Mendelian randomisation (MR) to assess causal roles in aetiology, we identify both shared and distinct effects of specific proteins across immune-mediated diseases, including directionally discordant roles for CD40 in rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease. MR implicates CXCL5 in the aetiology of ulcerative colitis (UC) and we show elevated gut CXCL5 transcript expression in UC patients. Our results highlight targets of existing drugs and provide a powerful resource to facilitate future drug target prioritisation.