Genetic and sociodemographic factors associated with trajectories of physical and mental health multimorbidity in a South Asian cohort in the UK: A multistate modelling analysis

by Daniel Stow, Ruby S. M. Tsang, Ioanna K. Katzourou, Qinqin Huang, Miriam Samuel, Megan L. Wood, Jack F. G. Underwood, Genes and Health Research Team, The LIfespaN multimorbidity research Collaborative (LINC) , Rupert A. Payne, James T. R. Walters, Nicholas J. Timpson, Inês Barroso, Hilary C. Martin, Peter A. Holmans, Marianne B. M. van den Bree, Rohini Mathur, Sarah Finer Background UK South Asian populations are at high risk of physical and mental health multimorbidity, which means they live with multiple long-term conditions. The life course emergence of multimorbidity, its underlying aetiology, and consequences for future health and mortality have yet to be studied in this population. Methods and findings We studied Internalising (depression, anxiety, somatoform disorders) and Cardiometabolic (hypertension, obesity, type 2 diabetes, chronic kidney disease, dyslipidaemia) MultiMorbidity (ICM-MM): the lifetime occurrence of ≥1 internalising mental health condition AND ≥1 cardiometabolic condition in a longitudinal cohort of Genes and Health study participants with linked genetic and health data from 1st April 1997–24th November 2024. We used multi-state models to investigate trajectories in ICM-MM and risk of major cardiovascular or renal events (CVR) or non-CVR death. We used flexible parametric models to estimate baseline hazards for health state transitions, adjusting for sociodemographic factors, a polygenic risk score (PRS) for ICM-MM (ICM-MM PRS ), and describe 10-year simulated health state probabilities. Over 10.2 years median follow-up of 23,554 British Bangladeshi and Pakistani participants (median baseline age 31.1 years, 12,934 [54.9%] women), 3,159 (13.4%) developed ICM-MM; 1,522 (6.5%) CVR; and there were 103 (0.4%) non-CVR deaths. Women were less likely to remain healthy, with higher probability of developing internalising conditions and subsequent ICM-MM, but lower risk of CVR than men. Younger age was associated with higher risk of developing internalising conditions. Bangladeshi ethnicity, higher deprivation, and smoking were all associated with higher probability of ICM-MM. 10-year CVR risk was highest for people who developed ICM-MM via the trajectory cardiometabolic-to-internalising (versus internalising-to-cardiometabolic) in mid-life (age 40). Higher ICM-MM PRS was associated with higher probability of ICM-MM via cardiometabolic conditions rather than internalising conditions. Our findings are based on routinely collected electronic health records from East London, which incompletely capture individual-level and time-varying risk factors, remission or recovery, and may not reflect British Bangladeshi and British Pakistani communities across the UK. The PRS was derived largely from GWAS of European ancestry populations, which may limit its transferability to this cohort. Conclusions The burden of multimorbidity is high in British Bangladeshi and British Pakistani populations. Young Bangladeshi women are at high risk of ICM-MM, while men are at higher risk of CVR. Detection and intervention strategies for physical and mental health multimorbidity should be targeted early in the lifecourse, for those at highest risk.