Genome-wide association study identifies a role for the progesterone receptor in benign prostatic hyperplasia risk.

Prostate Cancer and Prostatic Diseases
Weiqiang Li, Robert J Klein

Abstract

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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Software Mentioned

eMERGE
IMPUTE2
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