Proteome-wide association study of prostate cancer risk across populations
Abstract
Abstract 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.
Article Details
Authors (22)
Hua Zhong
Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore 117543, Republic of Singapore
Jingjing Zhu
State Key Laboratory of Advanced Fiber Materials, College of Chemistry and Chemical Engineering
Shuai Liu
College of Materials Science and Engineering
Chong Wu
Liang Wang
Seamus P. Whelton
Catherine H. Marshall
Michael J. Blaha
Peter Durda
Department of Pathology and Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
Xiuqing Guo
Craig W. Johnson
Henry J. Lin
Kent D. Taylor
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
Russell P. Tracy
Laboratory for Clinical Biochemistry Research, Larner College of Medicine, University of Vermont, Burlington, VT, USA.
Ronit I. Yarden
Ani W. Manichaikul
Department of Genome Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Stephen S. Rich
Department of Genome Sciences, School of Medicine, University of Virginia, Charlottesville, VA, USA.
Jerome I. Rotter
Rajat Deo
Ruth F. Dubin
Peter Ganz
Lang Wu