title: Pleiotropy and pathway analyses of genetic variants associated with both type 2 diabetes and prostate cancer.
abstract: OBJECTIVE
  Epidemiological evidence shows that diabetes is associated with a reduced risk of prostate cancer. The objective of this study was to identify genes that may contribute to both type 2 diabetes and prostate cancer outcomes and the biological pathways these diseases may share.
  
  
  METHODS
  The Atherosclerosis Risk in Communities (ARIC) Study is a population-based prospective cohort study in four U.S. communities that included a baseline examination in 1987-89 and three follow-up exams at three year intervals. Participants were 45-64 years old at baseline. We conducted a genomewide association (GWA) study of incident type 2 diabetes in males, summarized variation across genetic loci into a polygenic risk score, and determined if that diabetes risk score was also associated with incident prostate cancer in the same study population. Secondarily we conducted a separate GWA study of prostate cancer, performed a pathway analysis of both type 2 diabetes and prostate cancer, and qualitatively determined if any of the biochemical pathways identified were shared between the two outcomes.
  
  
  RESULTS
  We found that the polygenic risk score for type 2 diabetes was not statistically significantly associated with prostate cancer. The pathway analysis also found no overlap between pathways associated with type 2 diabetes and prostate cancer. However, it did find that the growth hormone signaling pathway was statistically significantly associated with type 2 diabetes (p=0.0001).
  
  
  CONCLUSIONS
  The inability of this study to find an association between type 2 diabetes polygenic risk scores with prostate cancer or biological pathways in common suggests that shared genetic variants may not contribute significantly to explaining shared etiology.
authors.affiliation: Division of Academic General Pediatrics, Department of Pediatrics, University of Minnesota Minneapolis, MN.
authors.forename: L A
authors.initials: LA
authors.lastname: Raynor
authors.forename: James S
authors.initials: JS
authors.lastname: Pankow
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Rasmussen-Torvik
authors.forename: Weihong
authors.initials: W
authors.lastname: Tang
authors.forename: Anna
authors.initials: A
authors.lastname: Prizment
authors.forename: David J
authors.initials: DJ
authors.lastname: Couper
keywords: Type 2 diabetes; pathway analysis; polygenic risk score; prostate cancer
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