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Pleiotropic Analysis of Lung Cancer and Blood Triglycerides
Verena Zuber1, Crystal N Marconett1, Jianxin Shi1
1NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine (VZ, AW, FB, YW, OAA), and Prostate Cancer Research Group, Centre for Molecular Medicine Norway, Nordic EMBL Partnership (VZ, IGM), University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway (VZ, AW, FB, YW, OAA); European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK (VZ); Departments of Surgery and of Biochemistry and Molecular Biology (CNM, CY, IALO) and Will Rogers Institute Pulmonary Research Center and Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine (BZ, ZB), Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA (CNM, CY, IALO); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, US Public Health Service, Bethesda, MD (JS, XH, LS, DA, NEC, NC, MTL); Information Management Services, Inc.; Rockville, MD (WW); Multimodal Imaging Laboratory (AMD, AJS), Center for Human Development (AMD, AJS), Department of Radiology (AMD), Department of Neurosciences (AMD), Department of Psychiatry (WKT), and Cognitive Sciences Graduate Program (AJS), University of California, San Diego, La Jolla, CA; Division of Epigenomics and Cancer Risk Factors, German Cancer Research Center (DKFZ), Heidelberg, Germany (ML, AR); Department of Molecular Biology, University of Salzburg, Salzburg, Austria (AR); Translational Lung Research Center Heidelberg TLRC-H, Member of the German Center for Lung Research DZL, Heidelberg, Germany (AR); Department of Medical Genetics (SD) and Department of Molecular Oncology, Institute of Cancer Research and Department of Urology (IGM), Oslo University Hospital, Oslo, Norway (SD); NORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway (SD); Radboud Unive
Abstract:
Epidemiologically related traits may share genetic risk factors, and pleiotropic analysis could identify individual loci associated with these traits. Because of their shared epidemiological associations, we conducted pleiotropic analysis of genome-wide association studies of lung cancer (12 160 lung cancer case patients and 16 838 control subjects) and cardiovascular disease risk factors (blood lipids from 188 577 subjects, type 2 diabetes from 148 821 subjects, body mass index from 123 865 subjects, and smoking phenotypes from 74 053 subjects). We found that 6p22.1 (rs6904596, ZNF184) was associated with both lung cancer (P = 5.50x10(-6)) and blood triglycerides (P = 1.39x10(-5)). We replicated the association in 6097 lung cancer case patients and 204 657 control subjects (P = 2.40 × 10(-4)) and in 71 113 subjects with triglycerides data (P = .01). rs6904596 reached genome-wide significance in lung cancer meta-analysis (odds ratio = 1.15, 95% confidence interval = 1.10 to 1.21 ,: Pcombined = 5.20x10(-9)). The large sample size provided by the lipid GWAS data and the shared genetic risk factors between the two traits contributed to the uncovering of a hitherto unidentified genetic locus for lung cancer.
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