Social, lifestyle, and genetic determinants of multimorbidity clusters in middle-aged and older Canadian adults: an analysis of the clsa data

Abstract

Background: Multimorbidity, defined as the co-occurrence of two or more chronic conditions, is increasingly prevalent among aging populations. Although lifestyle and socioeconomic factors contribute substantially, the genetic underpinnings of multimorbidity remain poorly understood. Objectives: This thesis aimed to identify the most common multimorbidity (MCM) among middle-aged and older Canadian adults, and to investigate the prevalence, associated risk factors, and genetic susceptibility of MCM. Methods: This study included 30,097 participants from the comprehensive cohort of the Canadian Longitudinal Study on Aging. Survey-specific multivariate logistic regression was used to identify significant risk factors of MCM. A polygenic risk score (PRS) was derived for each participant. The modification effects of the PRS on the association between age and risk of MCM were examined by a Genome-wide interaction study. Results: Osteoarthritis–hypertension emerged as the MCM with a prevalence of 16.5% among middle-aged and older Canadian adults. Seven factors including increasing age, retirement, poor perceived health, sleep problems, obesity, urban core residence, and living in eastern provinces were significantly associated with increased risk of MCM. Ten genetic variants with an interaction term p-value <10-5 were selected to be included in the calculation of PRS for each participant. The participants in the top PRS tercile (top 1/3 PRS) exhibited the greatest risk of MCM. For each additional year of age, MCM risk increased by 13% (Adjusted Odds Ratio (AOR)=1.13, 95% Confidence Interval (CI): 1.11 – 1.15) in the top-PRS group compared with 9% (AOR=1.09, 95%CI: 1.07 – 1.12) in the middle PRS tercile and 10% (AOR=1.10, 95%CI: 1.08 – 1.12) in the low PRS tercile group. Conclusion: Both social-environmental and genetic determinants jointly influence multimorbidity, highlighting the need for integrated prevention strategies and precision aging interventions in Canada.