Landscape of stroke comorbidities: A disease-wide association study

Abstract

Stroke is a leading cause of death and disability worldwide, with diverse comorbidities that influence its clinical outcomes. However, a comprehensive understanding of the short- and long-term patterns of stroke-related comorbidities remains limited. To address this gap, we conducted a disease-wide association study (DWAS) to systematically explore the landscape of stroke comorbidities in a population-based cohort. Using data from the FinnGen cohort, which included 337,194 participants and 27,496 ischemic stroke cases, we analyzed 1,757 medical events as potential stroke comorbidities. We employed Cox proportional hazards regression, adjusting for sex and age, to identify significant associations between stroke and these medical events. Comorbidities were classified into pre- and post-stroke categories, and their temporal patterns were analyzed over a 1- to 15-year follow-up period. Our findings revealed that stroke comorbidities span multiple disease taxonomies, with significant enrichment in the circulatory, digestive, and musculoskeletal systems. Notably, the study identified distinct pre-stroke and post-stroke comorbidities that persist or evolve over time, supporting the concept of a disease continuum. These temporal patterns suggest that stroke risk and outcomes are shaped by sequential comorbidities rather than simultaneous occurrences. This study provides the most comprehensive profile of stroke comorbidities to date, highlighting the interconnected nature of diseases. By mapping the progression of comorbidities across time and disease categories, DWAS offers valuable insights for early intervention and long-term treatment. Our findings emphasize the importance of viewing stroke as part of a broader disease continuum, offering new opportunities for prevention, diagnosis, and treatment strategies tailored to individual risk profiles.