Fig. 3: Observational analyses and MR analyses between candidate proteins and inflammatory bowel disease and its subtypes.

The forest plots showed the results of observational analyses and MR analyses between candidate proteins and (a) inflammatory bowel disease, (b) Crohn’s disease, and (c) ulcerative colitis. Cox regression was used to evaluate the association between baseline plasma protein and the incidence of IBD and its subtypes during study follow-up in UKB-PPP study (baseline participants: n = 48,800; incident IBD events: n = 336; incident CD events: n = 125; incident UC events: n = 232) adjusted for age, sex, assessment center, education, employment status, household income, TDI, smoking status, alcohol consumption, PA, healthy diet, sleep during, and BMI. The measure of centre and error bars in observational analyses presented the HRs and 95% CI of IBD and its subtypes risk increase associated with per 1-SD higher protein level. MR analysis, including Wald ratio or inverse variance weighted method, was used to evaluate the association between cis-pQTLs from UKB-PPP and IBD and its subtypes from IIBDGC (with results shown in green) and FinnGen (with results shown in purple). Meta-analysis was used to combine MR analysis results of IIBDGC and FinnGen (with results shown in red). The measure of centre and error barsin in MR analyses presented the ORs and 95% CI of IBD and its subtypes per 1-SD higher protein level for these proteins from in MR analyses. All tests were two sided and adjusted for multiple comparisons, with an FDR < 0.05 considered as significant. UKB-PPP UK Biobank Pharma Proteomics Project, IIBDGC International Inflammatory Bowel Disease Genetics Consortium, HR hazard ratio, OR odds ratio, CI confidence interval. Source data are provided as Supplementary Data 1, 9, and Source Data file.