Open AccessUterine fibroid polygenic risk score (PRS) associates and predicts risk for uterine fibroid
Author(s) -
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 M. Roden,
Josh C. Denny,
Todd L. Edwards,
Digna R. Velez Edwards
Publication year - 2022
Publication title -
human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.351
H-Index - 137
eISSN - 1432-1203
pISSN - 0340-6717
DOI - 10.1007/s00439-022-02442-z
Subject(s) - genome wide association study , linkage disequilibrium , biology , logistic regression , uterine fibroids , receiver operating characteristic , confidence interval , genetic association , population , medicine , oncology , gynecology , genetics , single nucleotide polymorphism , genotype , environmental health , gene
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 p t < 0.001 and after linkage disequilibrium pruning (r 2 < 0.2), 4458 variants were in the PRS which was significant (pseudo-R 2 = 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.