Chronic prostatitis/chronic pelvic pain syndrome is common, and it impacts men's health and quality of life. The genetic basis of this condition remains largely unknown. Here, we conduct a GWAS using data from the Million Veteran Program of over 590,000 men of European, African, and Hispanic ancestry, including 14,575 chronic prostatitis/chronic pelvic pain syndrome cases. The multi-ancestry analysis identifies eight novel loci associated with chronic prostatitis/chronic pelvic pain syndrome risk, an increase from three significant genome-wide loci found in the European participants alone. We also estimate the genetic correlations between chronic prostatitis/chronic pelvic pain syndrome and 12 phenotypes. Notably, the genetic correlation between chronic prostatitis/chronic pelvic pain syndrome and prostate cancer is not significant. Further, Mendelian randomization shows a significant, potentially bidirectional causal relationship between chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia, but not between chronic prostatitis/chronic pelvic pain syndrome and prostate cancer, suggesting a complex interplay between chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia. Results of bivariate causal mixture modeling indicate that some of the same genetic variants likely contribute to the development of chronic prostatitis/chronic pelvic pain syndrome, benign prostatic hyperplasia, and prostate cancer.
Nature communications. 2026 Jan 09*** epublish ***
Sara Brin Rosenthal, Adam X Maihofer, Caroline M Nievergelt, Daniel Dochtermann, Armand Gerstenberger, Thomas Whisenant, Saiju Pyarajan, Kristina Allen-Brady, John N Krieger, Million Veteran Program , Niloofar Afari, Marianna Gasperi
Center for Computational Biology & Bioinformatics, Department of Medicine, University of California San Diego, La Jolla, CA, USA., VA San Diego Healthcare System (VASDHS), San Diego, CA, USA., Center for Data and Computational Sciences (C-DACS), VA Boston Healthcare System (VABHS), Boston, MA, USA., VA Puget Sound Health Care System (VAPSHCS), Seattle, WA, USA., Division of Epidemiology, Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA., Department of Urology, University of Washington School of Medicine, Seattle, WA, USA., VA San Diego Healthcare System (VASDHS), San Diego, CA, USA. .