Genome-wide associations for benign prostatic hyperplasia reveal a genetic correlation with serum levels of PSA

Nat Commun. 2018 Nov 8;9(1):4568. doi: 10.1038/s41467-018-06920-9.


Benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) are common conditions affecting the majority of elderly males. Here we report the results of a genome-wide association study of symptomatic BPH/LUTS in 20,621 patients and 280,541 controls of European ancestry, from Iceland and the UK. We discovered 23 genome-wide significant variants, located at 14 loci. There is little or no overlap between the BPH/LUTS variants and published prostate cancer risk variants. However, 15 of the variants reported here also associate with serum levels of prostate specific antigen (PSA) (at a Bonferroni corrected P < 0.0022). Furthermore, there is a strong genetic correlation, rg = 0.77 (P = 2.6 × 10-11), between PSA and BPH/LUTS, and one standard deviation increase in a polygenic risk score (PRS) for BPH/LUTS increases PSA levels by 12.9% (P = 1.6×10-55). These results shed a light on the genetic background of BPH/LUTS and its substantial influence on PSA levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Aged
  • Computational Biology
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Histones / metabolism
  • Humans
  • Iceland
  • Lower Urinary Tract Symptoms / blood
  • Lower Urinary Tract Symptoms / genetics
  • Lysine / metabolism
  • Male
  • Meta-Analysis as Topic
  • Multifactorial Inheritance / genetics
  • Mutation / genetics
  • Phenotype
  • Prostate-Specific Antigen / blood*
  • Prostatic Hyperplasia / blood*
  • Prostatic Hyperplasia / genetics*
  • Quantitative Trait Loci / genetics
  • Risk Factors
  • United Kingdom


  • Histones
  • Prostate-Specific Antigen
  • Lysine