A Phenome-Wide Association Study of Uterine Fibroids Reveals a Marked Burden of Comorbidities

Abstract

Abstract The burden of comorbidities in those with uterine fibroids compared to those without fibroids is understudied. We performed a phenome-wide association study to systematically assess the association between fibroids and other conditions. Vanderbilt University Medical Center’s Synthetic Derivative and Geisinger Health System Database, two electronic health record databases, were used for discovery and validation. Non-Hispanic Black and White females were included. Fibroid cases were identified through a previously validated algorithm. Race-stratified and cross-ancestry analyses, adjusting for age and body mass index, were performed before significant, validated results were meta-analyzed. There were 52,200 and 26,918 (9,022 and 10,232 fibroid cases) females included in discovery and validation analyses. In cross-ancestry meta-analysis, 389 conditions were associated with fibroid risk with evidence of enrichment of circulatory, dermatologic, genitourinary, musculoskeletal, and sense organ conditions. The strongest associations within and across racial groups included conditions previously associated with fibroids. Numerous novel diagnoses, including cancers in female genital organs, were tied to fibroid status. Overall, individuals with fibroids had a marked increase in comorbidities compared to those without fibroids. This novel approach to evaluate the health context of fibroids highlights the potential to understand fibroid etiology through studying common biology of comorbid diagnoses and through disease networks.