• Ole A Andreassen, Verena Zuber, Wesley K Thompson, Andrew J Schork, Francesco Bettella, PRACTICAL Consortium, CRUK GWAS, Srdjan Djurovic, Rahul S Desikan, Ian G Mills, and Anders M Dale.
• NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway, Prostate Cancer Research Group, Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway, Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA, Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, USA, Cognitive Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA, Center for Human Development, University of California at San Diego, La Jolla, CA, USA, the participants acknowledged in Supplementary data, available at IJE online, Department of Medical Genetics, Oslo University Hospital, Oslo, Norway, Department of Radiology, University of California, San Diego, La Jolla, CA, USA, Department of Cancer Prevention, Institute of Cancer Research and Department of Urology, Oslo University Hospital, Oslo, Norway and Department of Neurosciences, University of California, San Diego, La Jolla, CA, USANORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway, Prostate Cancer Research Group, Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo and Oslo University Hospital, Oslo, Norway, Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA, Multimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, USA, Cognitive Sciences Graduate Program, University of California, San Diego, La Jolla, CA, USA, Center for Human Development, University of California at San Diego, La Jolla, CA, USA, the participants acknowledged in Supplementary data, available at IJE online, Department of Medical Genetics, Oslo University Hospital, Oslo
• Int J Epidemiol. 2014 Aug 1; 43 (4): 1205-14.

BackgroundEpidemiological and clinical studies suggest comorbidity between prostate cancer (PCA) and cardiovascular disease (CVD) risk factors. However, the relationship between these two phenotypes is still not well understood. Here we sought to identify shared genetic loci between PCA and CVD risk factors.MethodsWe applied a genetic epidemiology method based on conjunction false discovery rate (FDR) that combines summary statistics from different genome-wide association studies (GWAS), and allows identification of genetic overlap between two phenotypes. We evaluated summary statistics from large, multi-centre GWA studies of PCA (n=50 000) and CVD risk factors (n=200 000) [triglycerides (TG), low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, systolic blood pressure, body mass index, waist-hip ratio and type 2 diabetes (T2D)]. Enrichment of single nucleotide polymorphisms (SNPs) associated with PCA and CVD risk factors was assessed with conditional quantile-quantile plots and the Anderson-Darling test. Moreover, we pinpointed shared loci using conjunction FDR.ResultsWe found the strongest enrichment of P-values in PCA was conditional on LDL and conditional on TG. In contrast, we found only weak enrichment conditional on HDL or conditional on the other traits investigated. Conjunction FDR identified altogether 17 loci; 10 loci were associated with PCA and LDL, 3 loci were associated with PCA and TG and additionally 4 loci were associated with PCA, LDL and TG jointly (conjunction FDR <0.01). For T2D, we detected one locus adjacent to HNF1B.ConclusionsWe found polygenic overlap between PCA predisposition and blood lipids, in particular LDL and TG, and identified 17 pleiotropic gene loci between PCA and LDL, and PCA and TG, respectively. These findings provide novel pathobiological insights and may have implications for trials using targeting lipid-lowering agents in a prevention or cancer setting.© The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

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