The impact of genetic and sociodemographic factors on life course trajectories of physical-mental health multimorbidity in a UK South Asian cohort

BackgroundUK South Asian populations have a high risk of many cardiometabolic and internalising mental health conditions such as depression and anxiety, and they commonly co-exist as physical and mental health multimorbidity. However, the emergence of this multimorbidity across the lifecourse, and its underlying aetiology, is rarely studied. MethodsWe studied Internalising and Cardiometabolic MultiMorbidity (ICM-MM) in a longitudinal cohort with linked genetic and health data from Genes & Health. ICM-MM was defined as lifetime occurrence of > 1 internalising condition AND > 1 cardiometabolic condition. Using multi state models, we investigated ICM-MM trajectories and their effect on risk of cardiovascular event (CVE) or death, accounting for competing risks. We used flexible parametric models to estimate baseline hazards for transitions between health states, adjusting for gender, age, ethnicity, deprivation, smoking, and a novel polygenic risk score for ICM-MM (ICM-MMPRS) FindingsIn our cohort of 25,641 British Bangladeshi and Pakistani people (median follow-up 10.5 years, median age 31.1 years at cohort entry), women had higher risk of internalising conditions and subsequent ICM-MM, whilst men were at higher risk of CVE. Younger age was associated with higher risk of internalising conditions. Bangladeshi ethnicity, deprivation, and smoking were all associated with higher ICM-MM risk. 10-year CVE risk was higher for transitioning from cardiometabolic morbidity to ICM-MM in midlife than internalising morbidity to ICM-MM. ICM-MMPRS was associated with higher risk of transitioning from cardiometabolic morbidity to ICM-MM than internalising morbidity to ICM-MM. InterpretationThe burden of multimorbidity is high in the population and develops at an early age. Young Bangladeshi women are at highest risk of ICM-MM, while men are at higher risk of CVE. Detection and intervention strategies for physical-mental health multimorbidity targeted early in the lifecourse, for those at risk. Funding: MRC[MR/W014416/1]