Disease-wide association study uncovers disease continuum network of unipolar depression

Unipolar depression is typically regarded as a psychiatric disorder, yet it frequently coexists with various major diseases. This study employs a Disease-Wide Association Study (DWAS) approach to map the disease continuum surrounding unipolar depression, analyzing data from a registry cohort of 392,423 individuals, including 43,280 diagnosed cases of unipolar depression. Significant associations were identified between depression and comorbidities across multiple organ systems, including both mental and physical disorders. Next, temporal analysis categorized these comorbidities based on their onset relative to depression into short-term (1-year), mid-term (5-year), and long-term (15-year) periods, discovering temporal consistent associations with comorbidities such as schizophrenia, anxiety disorders, post-traumatic stress disorder (PTSD), asthma, hypothyroidism, type 2 diabetes, cardiac arrhythmias, and cancer. These findings highlight the interconnected nature of depression within a broader disease continuum network. Recognizing depression within this systemic framework supports the adoption of personalized medicine strategies tailored to individual comorbidity profiles, enabling therapeutic targeting of shared pathogenic mechanisms that concurrently address both depression and its associated comorbidities.