Life-course body size trajectories and polygenic risk for incident inflammatory bowel disease

Life-course body size dynamics may contribute to inflammatory bowel disease (IBD) risk, but whether distinct anthropometric trajectories add information beyond adult body mass index (BMI) and inherited susceptibility remains unclear. We included 486,449 UK Biobank participants free of IBD at baseline; trajectory analyses were restricted to 262,601 participants with complete self-reported birth weight, recalled childhood body size at age 10 years, and measured baseline BMI, and joint trajectory–polygenic risk score (PRS) analyses included 254,481 participants with complete trajectory and PRS data. During a median follow-up of 14.7 years, 1,722 participants developed Crohn’s disease (CD) and 3,340 developed ulcerative colitis (UC) in the eligible cohort. Group-based trajectory modelling identified five trajectories. Compared with the stable Normal–Average–Normal trajectory, Normal–Thinner–Overweight/obesity and Macrosomia–Average–Overweight/obesity showed modest nominal associations with higher UC risk, whereas comparable associations were not observed for CD. In PRS-stratified trajectory analyses, relative hazard ratios for UC appeared elevated for several non-reference trajectories in the low-PRS stratum, but estimates were imprecise because of sparse events in the reference cell and absolute risk differences were modest. These findings provide hypothesis-generating evidence that life-course body-size patterning may be related to adult-onset UC more than CD, but interpretation is limited by missing trajectory data, retrospective recall of early-life body size, multiple testing, sparse stratified events, and health-record-based outcome ascertainment.