PROJECT SUMMARY RELEVANCE: Approximately 1 in 4 U.S. adults suffers from multimorbidity, or two or more concurrent chronic diseases. People with multimorbidity experience more disability and higher mortality risk and have higher medical costs than people with 1 chronic condition. Our understanding of the onset and progression of multimorbidity is limited. OBJECTIVES: To develop clinical practice guidelines and interventions, it is necessary to have accurate information about the progression of multimorbidity, the age and timing of onset, and differences in these across population groups. AIMS: 1) Harmonize and bridge national longitudinal data to track the incidence of chronic diseases and multimorbidity in the U.S. starting at age 30. We will combine 7 premier national cohort datasets of adult health (Add Health, NLSY79, NLSY97, PSID, REGARDS, H-EPESE, HRS) to create a synthetic nationally representative cohort of adults starting at age 30 years, compiling over 1.7 million person-years of follow-up and include sizeable number of racial/ethnic minorities. 2) Estimate the progression to multimorbidity starting at age 30 years. We will identify the age-specific progression rate of common chronic disease clusters and the sentinel conditions associated with higher risks of progression to additional diseases. 3) Develop measures of age-specific risk of multimorbidity for the US adult population and calculate the lifetime risk of developing multimorbidity and years spent with multimorbidity. 4) For major race-ethnic, sex, economic, and geographic groups, identify the sentinel conditions, age-specific progression, and lifetime risk of multimorbidity. We will estimate differences across groups and quantify the implications of reducing these disparities on disease-free life expectancy, with the additional innovation of adjusting for biases due to differential mortality and institutionalization. DESIGN: Bridging and reweighting procedures will be applied to develop a new data infrastructure with nationally representative longitudinal birth cohorts and synthetic cohorts. We will use Poisson regression to model the ages at which disparities in multi-morbidity emerge. To capture the sequencing and pacing of multimorbidity, we will estimate the probability of experiencing an additional (k+1th) condition for those with k prior chronic conditions. We will estimate cumulative probabilities based on Kaplan-Meier survival probabilities. Disparities will be quantified using Greenwood’s estimator. IMPACT: This project will advance understanding of the nature, onset, and progression of multimorbidity. To inform clinical practice and healthcare guidelines, we will identify conditional risks of transitioning to additional diseases given age of onset and sentinel disease. With particular relevance to policy, we will model the years of disease-free life expectancy that would be gained by interventions that delay or avert the onset of sentinel diseases. The data infrastruc...