Uterine fibroid polygenic risk score (PRS) associates and predicts risk for uterine fibroid

Jacqueline A. Piekos, Jacklyn N. Hellwege, Yanfei Zhang, Eric S. Torstenson, Gail P. Jarvik, Ozan Dikilitas, Iftikhar J. Kullo, Daniel J. Schaid, David R. Crosslin, Sarah A. Pendergrass, Ming Ta Michael Lee, Dan Roden, Josh C. Denny, Todd L. Edwards, Digna R. Velez Edwards

Research output: Contribution to journalArticlepeer-review


Uterine fibroids (UF) are common pelvic tumors in women, heritable, and genome-wide association studies (GWAS) have identified ~ 30 loci associated with increased risk in UF. Using summary statistics from a previously published UF GWAS performed in a non-Hispanic European Ancestry (NHW) female subset from the Electronic Medical Records and Genomics (eMERGE) Network, we constructed a polygenic risk score (PRS) for UF. UF-PRS was developed using PRSice and optimized in the separate clinical population of BioVU. PRS was validated using parallel methods of 10-fold cross-validation logistic regression and phenome-wide association study (PheWAS) in a seperate subset of eMERGE NHW females (validation set), excluding samples used in GWAS. PRSice determined pt < 0.001 and after linkage disequilibrium pruning (r2 < 0.2), 4458 variants were in the PRS which was significant (pseudo-R2 = 0.0018, p = 0.041). 10-fold cross-validation logistic regression modeling of validation set revealed the model had an area under the curve (AUC) value of 0.60 (95% confidence interval [CI] 0.58–0.62) when plotted in a receiver operator curve (ROC). PheWAS identified six phecodes associated with the PRS with the most significant phenotypes being 218 ‘benign neoplasm of uterus’ and 218.1 ‘uterine leiomyoma’ (p = 1.94 × 10–23, OR 1.31 [95% CI 1.26–1.37] and p = 3.50 × 10–23, OR 1.32 [95% CI 1.26–1.37]). We have developed and validated the first PRS for UF. We find our PRS has predictive ability for UF and captures genetic architecture of increased risk for UF that can be used in further studies.

Original languageEnglish (US)
Pages (from-to)1739-1748
Number of pages10
JournalHuman genetics
Issue number11
StatePublished - Nov 2022

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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