Global trends in the burden of inflammatory bowel disease from 1990 to 2021: socioeconomic and sex-specific disparities with exploratory mendelian randomization analyses

Inflammatory bowel disease (IBD) shows substantial variation in burden across regions and populations worldwide. However, patterns of IBD b3urden across levels of socio-demographic development remain incompletely characterized, and complementary evidence on selected individual-level exposures is limited. Utilizing GBD 2021 data, we assessed age-standardized incidence rate (ASIR), prevalence rate (ASPR), mortality rate (ASMR), and disability-adjusted life years rate (ASDR) from 1990 to 2021 across socio-demographic index (SDI) strata. Temporal trends were estimated using estimated annual percentage change and Joinpoint regression. Pearson analysis and frontier analyses assessed SDI correlations, while inequality was measured using the concentration index and slope index. Decomposition analysis was performed to identify the contributors of population growth, population aging, and epidemiological change. Two-sample Mendelian randomization (MR) analysis was conducted to examine potential associations between selected exposures and IBD. From 1990 to 2021, the global ASIR rose by 0.29 annually, while ASPR, ASMR and ASDR decreased by 0.13, 0.31 and 0.52. Burden patterns differed across SDI strata. High SDI regions had the highest age-standardized burden in 2021. The largest increases in ASIR and ASPR were observed in middle SDI regions, and declines in ASMR and ASPR began later in low SDI regions than in high SDI regions. ASDR was positively correlated with SDI in females but not in males, and cross-country inequality in ASDR was greater in females than in males. Decomposition analysis showed that population aging contributed more to changes in ASMR and ASDR in high SDI regions, while population growth was the dominant contributor in low SDI regions. Fifteen countries showed large effective differences between observed ASDR and frontier values at comparable SDI levels. In MR analyses, several nominal associations were observed, but none remained significant after false discovery rate (FDR) correction. The burden of IBD showed substantial heterogeneity across SDI levels and between sexes in GBD 2021, with a more pronounced inequality pattern in disability burden among women. The MR findings did not remain significant after FDR correction and should therefore be interpreted cautiously as exploratory signals. These findings underscore the importance of context-specific strategies to reduce inequalities in IBD burden across populations and between women and men.