Journal Article

A phenome-wide association study of uterine fibroids reveals a marked burden of comorbidities

Pendergrass, Sarah A., Jones, Sarah H., Hellwege, Jacklyn N., Torstenson, Eric S., Jasper, Elizabeth A., Zhang, Yanfei, Edwards, Todd L., Mautz, Brian S., Piekos, Jacqueline A., Lee, Ming Ta Michael, Velez Edwards, Digna R.

2025

Overview

Background 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. Methods 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 multi-population phenome-wide association analyses, adjusting for age and body mass index, were performed before statistically significant, validated results were meta-analyzed. Results There were 52,295 and 26,918 (9022 and 10,232 fibroid cases) females included in discovery and validation analyses. In multi-population 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. Conclusions Overall, individuals with fibroids have a marked increase in comorbidities compared to those without fibroids. This approach to evaluate the health context of fibroids highlights the potential to understand fibroid etiology through studying the common biology of comorbid diagnoses and through disease networks. Plain language summary Though many females have uterine fibroids, not enough is known about how fibroids affect people’s health compared to those who do not have them. We explored fibroids’ connection to many other health conditions using information from electronic health records and groups of people from different races. Across all groups, we found over 380 conditions were associated with fibroids. Many of these health issues were circulatory, skin, genital and urinary, musculoskeletal, and sense organ conditions. In addition to strong known associations, we also found many diagnoses that have not been associated with fibroids, like cancers in female genitals. Overall, individuals with fibroids have more health conditions compared to those without fibroids. Our approach can help us to understand causes and consequences of fibroids. Jasper and Mautz et al. systematically assess associations between uterine fibroids and hundreds of conditions using electronic health record databases. They identify numerous associations, both known and novel, and find that individuals with fibroids have more comorbidities compared to those without fibroids.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Portfolio
• Subject: 692/308/174 / 692/699/2732/2731 / Age / Algorithms / Asymptomatic / Body mass index / Comorbidity / Diabetes / Disease / Electronic health records / Ethnicity / Females / Fibroids / Hypertension / Medicine / Medicine & Public Health / Meta-analysis / Population / Risk factors / Self report