Comorbidity Profiles of Posttraumatic Stress Disorder Across the Medical Phenome

Background Prior epidemiological research has linked PTSD with specific physical health problems, but the comprehensive landscape of medical conditions associated with PTSD remains uncharacterized. Electronic health records (EHR) provide an opportunity to overcome prior clinical knowledge gaps and uncover associations with biological relevance that potentially vary by sex. Methods PTSD was defined among biobank participants (total N=123,365) in a major healthcare system using two ICD code-based definitions: broad (1+ PTSD or acute stress codes versus 0; N Case =14,899) and narrow (2+ PTSD codes versus 0; N Case =3,026). Using a phenome-wide association (PheWAS) design, we tested associations between each PTSD definition and all prevalent disease umbrella categories, i.e., phecodes. We also conducted sex-stratified PheWAS analyses including a sex-by-diagnosis interaction term in each logistic regression. Results A substantial number of phecodes were significantly associated with PTSD Narrow (61%) and PTSD Broad (83%). While top associations were shared between the two 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. Conclusions 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 EHR.