Comorbidity Profiles of Posttraumatic Stress Disorder Across the Medical Phenome

Previous epidemiological research has linked posttraumatic stress disorder (PTSD) with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records provide an opportunity to overcome clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex.

PTSD was defined among biobank participants (N = 145,959) in 3 major healthcare systems using 2 ICD code-based definitions: broad (≥1 PTSD or acute stress codes vs. 0; n _cases = 16,706) and narrow (≥2 PTSD codes vs. 0; n _cases = 3325). Using a phenome-wide association study design, we tested associations between each PTSD definition and all prevalent disease umbrella categories, i.e., phecodes. We also conducted sex-stratified phenome-wide association study analyses including a sex × diagnosis interaction term in each logistic regression.

A substantial number of phecodes were significantly associated with PTSD_Narrow (61%) and PTSD_Broad (83%). While the strongest associations were shared between the 2 definitions, PTSD_Broad captured 334 additional phecodes not significantly associated with PTSD_Narrow and exhibited a wider range of significantly associated phecodes across various categories, including respiratory, genitourinary, and circulatory conditions. Sex differences were observed in that PTSD_Broad was more strongly associated with osteoporosis, respiratory failure, hemorrhage, and pulmonary heart disease among male patients and with urinary tract infection, acute pharyngitis, respiratory infections, and overweight among female patients.

This study provides valuable insights into a diverse range of comorbidities associated with PTSD, including both known and novel associations, while highlighting the influence of sex differences and the impact of defining PTSD using electronic health records.