Proteome-wide association study of prostate cancer risk across populations
There is insufficient understanding of the molecular basis of prostate cancer (PCa) across different populations. We perform a large-scale proteome-wide association study (PWAS) to identify proteins with genetically regulated expression in plasma to be associated with PCa risk across populations. We develop genetic prediction models for expression of 1578, 1993, 1218, and 1390 proteins for African (n = 450), European (n = 758), Asian (n = 289), and Hispanic/Latino (n = 474) males, respectively, and evaluate associations of genetically regulated protein expression with PCa risk in 19,391 PCa cases and 61,608 controls of African population, 122,188 cases and 604,640 controls of European population, 10,809 cases and 95,790 controls of Asian population, and 3931 cases and 26,405 controls of Hispanic/Latino population. We identify three, four, 15, and 73 PCa-associated proteins in African, Hispanic/Latino, Asian, and European populations, respectively, and 83 in trans-population meta-analysis. There are both pan-population and population-specific associations. Our findings provide valuable insights into etiology of PCa.
Authors
- Ruth F. Dubin (ORCID: https://orcid.org/0000-0002-0498-1980)
- Michael Joseph Blaha (ORCID: https://orcid.org/0000-0001-5138-9683)
- Chong Wu (ORCID: https://orcid.org/0000-0002-8400-1785)
- Peter Durda
- Ani Manichaikul (ORCID: https://orcid.org/0000-0002-5998-795X)
- Jerome I. Rotter (ORCID: https://orcid.org/0000-0001-7191-1723)
- Jingjing Zhu (ORCID: https://orcid.org/0000-0002-9691-6034)
- Catherine Handy Marshall (ORCID: https://orcid.org/0000-0002-2653-4110)
- Ronit I. Yarden
- Rajat Deo (ORCID: https://orcid.org/0000-0002-8250-2607)
- Lang Wu (ORCID: https://orcid.org/0000-0001-9938-3627)
- Stephen S. Rich (ORCID: https://orcid.org/0000-0003-3872-7793)
- Peter Ganz (ORCID: https://orcid.org/0000-0002-0437-8882)
- Henry J. Lin (ORCID: https://orcid.org/0000-0001-6771-0486)
- W. Craig Johnson (ORCID: https://orcid.org/0000-0002-3161-3753)
- Seamus P. Whelton (ORCID: https://orcid.org/0000-0001-5914-0735)
- Xiuqing Guo (ORCID: https://orcid.org/0000-0002-5264-5068)
- Shuai Liu (ORCID: https://orcid.org/0000-0003-2244-2216)
- Liang Wang (ORCID: https://orcid.org/0000-0002-9364-8572)
- Kent D. Taylor
- Russell P. Tracy
- Hua Zhong (ORCID: https://orcid.org/0000-0003-3097-5717)
Institutions
- University of Vermont (US)
- University of Hawaiʻi at Mānoa (US)
- San Francisco General Hospital (US)
- The University of Texas MD Anderson Cancer Center (US)
- Johns Hopkins University (US)
- Hawaii Pacific University (US)
- University of Washington (US)
- UCLA Medical Center (US)
- Moffitt Cancer Center (US)
- The Coordinating Center (US)
- Cancer Center of Hawaii (US)
- National Heart, Lung, and Blood Institute (US)
- Johns Hopkins Hospital (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- Harbor–UCLA Medical Center (US)
- University of Virginia (US)
- Louisiana State University Health Sciences Center New Orleans (US)
- University of Pennsylvania (US)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-12-06
- DOI
- https://doi.org/10.1038/s41467-025-66250-5
- Primary Topic
- Prostate Cancer Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- National Human Genome Research Institute
- National Cancer Institute
- National Institute on Minority Health and Health Disparities