Benign prostatic hyperplasia (BPH) is common noncancerous prostate enlargement, which is usually associated with lower urinary tract symptoms (LUTS) and can lead to complex urinary, bladder, or kidney diseases. The majority of elderly men will be affected by BPH as age increases.
Here, we conducted a genome-wide association study (GWAS) of BPH using 1942 cases and 4730 controls from the Electronic Medical Records and Genomics network (eMERGE) as discovery cohort. We then used 5109 cases and 161,911 controls from UK Biobank as validation cohort.
This GWAS discovered 35 genome-wide significant variants (P < 5 × 10−8), located at 22 different loci in discovery cohort. We validated four significant variants located at four different loci in validation cohort: rs8027714 at 15q11.2, rs8136152 at 22q13.2, rs10192133 at 2q24.2, and rs1237696 at 11q22.1. rs1237696 is an intronic variant on chromosome 11 in the progesterone receptor (PGR) gene (P = 4.21 ×10–8, OR [95% CI] = 1.36 [1.22–1.52]). PGR is a known drug target for BPH as the PGR agonist gestonorone caproate has been used to treat BPH in multiple countries.
Our results suggest that genetic variants identified from BPH GWAS can identify pharmacologic targets for BPH treatment.
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Work in the Klein lab is supported by the National Cancer Institute (R01 CA175491). This work was supported in part through the computational resources and staff expertize provided by Scientific Computing at the Icahn School of Medicine at Mount Sinai, including infrastructure supported by the Office of Research Infrastructure of the National Institutes of Health under award number S10OD018522. We are grateful to the eMERGE network for making their data available through dbGaP phs000888.v1.p1. Specifically, we acknowledge a consortium of ten participating sites (Cincinnati Children’s Hospital Medical Center/Boston Children’s Hospital, Children’s Hospital of Philadelphia, Essentia Institute of Rural Health, Marshfield Clinic Research Foundation and Pennsylvania State University, Geisinger Clinic, Group Health Cooperative/University of Washington, Mayo Clinic, Icahn School of Medicine at Mount Sinai, Northwestern University, Vanderbilt University Medical Center) funded by the NHGRI. Assistance with phenotype harmonization and genotype data cleaning was provided by the eMERGE Administrative Coordinating Center (U01HG004603) and the National Center for Biotechnology Information (NCBI). We are also grateful to Ben Neale and the Neale Lab for making their analyses of the UK Biobank data freely available prior to publication.
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Li, W., Klein, R.J. Genome-wide association study identifies a role for the progesterone receptor in benign prostatic hyperplasia risk. Prostate Cancer Prostatic Dis (2020). https://doi.org/10.1038/s41391-020-00303-2