{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Piekos JA"],"funding":["NICHD NIH HHS","NHGRI NIH HHS","National Institutes of Health","National Human Genome Research Institute","NIH HHS","NIGMS NIH HHS"],"pagination":["1739-1748"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9420161"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["141(11)"],"pubmed_abstract":["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<sub>t</sub> < 0.001 and after linkage disequilibrium pruning (r<sup>2</sup> < 0.2), 4458 variants were in the PRS which was significant (pseudo-R<sup>2</sup> = 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<sup>-23</sup>, OR 1.31 [95% CI 1.26-1.37] and p = 3.50 × 10<sup>-23</sup>, 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."],"journal":["Human genetics"],"pubmed_title":["Uterine fibroid polygenic risk score (PRS) associates and predicts risk for uterine fibroid."],"pmcid":["PMC9420161"],"funding_grant_id":["K12 HD043483","U01HG8672","U01HG8673","U01HG006378","U01HG8676","R03 HD078567","T32 HG008341","T32GM080178","U01 HG008684","K12HD04348","U01 HG008685","U01 HG008664","U01HG6379","HG06379","U01HG8679","U01HG8657","U01 HG008666","U01 HG008701","T32 GM080178","R01HD074711","U01 HG006379","U01 HG006378","U01HG8680","R01 HD093671","R01HD093671","U01HG8684","U01 HG008680","U01HG8666","U01HG8685","U01 HG008672","U01 HG008673","U01HG8664","U01 HG008676","U01HG8701","R03HD078567","U01 HG011181","U01 HG008679","U01 HG008657","R01 HD074711"],"pubmed_authors":["Lee MTM","Velez Edwards DR","Dikilitas O","Crosslin DR","Schaid DJ","Roden D","Edwards TL","Piekos JA","Torstenson ES","Zhang Y","Hellwege JN","Jarvik GP","Kullo IJ","Pendergrass SA","Denny JC"],"additional_accession":[]},"is_claimable":false,"name":"Uterine fibroid polygenic risk score (PRS) associates and predicts risk for uterine fibroid.","description":"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<sub>t</sub> < 0.001 and after linkage disequilibrium pruning (r<sup>2</sup> < 0.2), 4458 variants were in the PRS which was significant (pseudo-R<sup>2</sup> = 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<sup>-23</sup>, OR 1.31 [95% CI 1.26-1.37] and p = 3.50 × 10<sup>-23</sup>, 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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-04T22:50:30.385Z","creation":"2025-04-04T22:50:30.385Z"},"accession":"S-EPMC9420161","cross_references":{"pubmed":["35226188"],"doi":["10.1007/s00439-022-02442-z"]}}