Bing Liu, Jue Xu, Caixia Jiang, Yan Zhang, Xin Wang
Poorer functional mobility was associated with CMM among middle-aged and older adults in China in both cross-sectional and longitudinal analyses. Simple functional assessments may help characterize groups with greater cardiometabolic burden and may be useful in clinical assessment and monitoring in ageing populations.
BACKGROUND: The co-occurrence of type 2 diabetes (T2D) and colorectal cancer (CRC) represents an increasing public health concern, contributing to greater clinical complexity and poorer outcomes. This study aimed to evaluate whether polygenic risk scores (PRS) for T2D and CRC are associated with the risk of T2D-CRC comorbidity and to investigate their potential interaction with body mass index (BMI).
METHODS: A Chinese cohort comprising four groups was analyzed, including individuals with both T2D and CRC (n = 202), T2D_only (n = 203), CRC_only (n = 199), and controls (n = 201). Ancestry-matched genome-wide association study data were used to construct PRS for T2D and CRC. Associations between genetic risk, adiposity, and disease status were assessed using multinomial logistic regression and multi-state models.
RESULTS: Individuals with T2D-CRC comorbidity exhibited higher PRS for both T2D and CRC compared with controls. In multinomial analyses, T2D PRS showed a borderline association with isolated CRC risk (OR = 1.24, P = 0.046). BMI significantly modified the association between CRC genetic liability and CRC risk (OR = 1.75, 95% CI: 1.27-2.34; P for interaction = 0.033), with stronger effects observed among overweight individuals. Multi-state modeling suggested that CRC genetic liability was associated with a higher hazard of transition from T2D to comorbidity (HR = 1.21, P = 0.037, FDR q = 0.150). Furthermore, individuals in the highest CRC PRS group showed a higher modeled probability of progressing to comorbidity by age 80 compared with those at lower genetic risk in exploratory cumulative risk analyses.
CONCLUSIONS: Genetic susceptibility to both T2D and CRC, together with adiposity, may help identify individuals at higher risk of developing comorbidity. Integrating PRS with BMI may provide a useful approach for risk stratification and support targeted prevention strategies in populations at elevated risk.