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Int J Mol Epidemiol Genet 2013;4(1):49-60
Original Article
Pleiotropy and pathway analyses of genetic variants associated with both type
2 diabetes and prostate cancer
LA Raynor, James S Pankow, Laura J Rasmussen-Torvik, Weihong Tang, Anna Prizment, David J Couper
Division of Academic General Pediatrics, Department of Pediatrics, University of Minnesota, Minneapolis, MN; Division of
Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; Department of
Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL; Department of Biostatistics, University
of North Carolina at Chapel Hill, Chapel Hill, NC
Received January 28, 2013; Accepted February 23, 2013; Epub March 18, 2013; Published March 28, 2013
Abstract: Aims: 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). Conclusion: 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. (IJMEG1301002).
Keywords: Type 2 diabetes, prostate cancer, polygenic risk score, pathway analysis
Address correspondence to: LA Raynor, Division of Academic General Pediatrics, Department of Pediatrics, University of
Minnesota, 717 Delaware St. SE Suite 353, 3rd Floor West, Minneapolis, MN 55414. Phone: 612-598-1148; Fax: 612-626-2134;
E-mail: rayno007@umn.edu
Original Article
Pleiotropy and pathway analyses of genetic variants associated with both type
2 diabetes and prostate cancer
LA Raynor, James S Pankow, Laura J Rasmussen-Torvik, Weihong Tang, Anna Prizment, David J Couper
Division of Academic General Pediatrics, Department of Pediatrics, University of Minnesota, Minneapolis, MN; Division of
Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN; Department of
Preventive Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL; Department of Biostatistics, University
of North Carolina at Chapel Hill, Chapel Hill, NC
Received January 28, 2013; Accepted February 23, 2013; Epub March 18, 2013; Published March 28, 2013
Abstract: Aims: 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). Conclusion: 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. (IJMEG1301002).
Keywords: Type 2 diabetes, prostate cancer, polygenic risk score, pathway analysis
Address correspondence to: LA Raynor, Division of Academic General Pediatrics, Department of Pediatrics, University of
Minnesota, 717 Delaware St. SE Suite 353, 3rd Floor West, Minneapolis, MN 55414. Phone: 612-598-1148; Fax: 612-626-2134;
E-mail: rayno007@umn.edu
