title: Genetic variants primarily associated with type 2 diabetes are related to coronary artery disease risk.
abstract: BACKGROUND
  The mechanisms underlying the association between diabetes and coronary artery disease (CAD) risk are unclear. We aimed to assess this association by studying genetic variants that have been shown to associate with type 2 diabetes (T2DM). If the association between diabetes and CAD is causal, we expected to observe an association of these variants with CAD as well.
  
  
  RESULTS
  We studied all genetic variants currently known to be associated with T2DM at a genome-wide significant level (p < 5*10(-8)) in CARDIoGRAM, a genome-wide data-set of CAD including 22,233 CAD cases and 64,762 controls. Out of the 44 published T2DM SNPs 10 were significantly associated with CAD in CARDIoGRAM (OR>1, p < 0.05), more than expected by chance (p = 5.0*10(-5)). Considering all 44 SNPs, the average CAD risk observed per individual T2DM risk allele was 1.0076 (95% confidence interval (CI), 0.9973-1.0180). Such average risk increase was significantly lower than the increase expected based on i) the published effects of the SNPs on T2DM risk and ii) the effect of T2DM on CAD risk as observed in the Framingham Heart Study, which suggested a risk of 1.067 per allele (p = 7.2*10(-10) vs. the observed effect). Studying two risk scores based on risk alleles of the diabetes SNPs, one score using individual level data in 9856 subjects, and the second score on average effects of reported beta-coefficients from the entire CARDIoGRAM data-set, we again observed a significant - yet smaller than expected - association with CAD.
  
  
  CONCLUSIONS
  Our data indicate that an association between type 2 diabetes related SNPs and CAD exists. However, the effects on CAD risk appear to be by far lower than what would be expected based on the effects of risk alleles on T2DM and the effect of T2DM on CAD in the epidemiological setting.
authors.affiliation: Deutsches Herzzentrum and DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Technische Universität München, Munich, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Jansen
authors.affiliation: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Loley
authors.affiliation: Institut für Epidemiologie, Universität zu Kiel, Kiel, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Durham, NC, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pencina
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK; Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, LE3 9QP, UK.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Nelson
authors.affiliation: Cardiovascular Research Center and Cardiology Division, Massachusetts General Hospital, Boston, MA, USA; Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA, USA.
authors.forename: Sekar
authors.initials: S
authors.lastname: Kathiresan
authors.affiliation: Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Gina M
authors.initials: GM
authors.lastname: Peloso
authors.affiliation: The Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Benjamin F
authors.initials: BF
authors.lastname: Voight
authors.affiliation: The Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.affiliation: Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Themistocles L
authors.initials: TL
authors.lastname: Assimes
authors.affiliation: University of Texas Health Science Center, Human Genetics Center and Institute of Molecular Medicine, Houston, TX, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.affiliation: Deutsches Herzzentrum and DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Technische Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Hengstenberg
authors.affiliation: Science Center, Tampere University Hospital, Tampere, Finland.
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
authors.affiliation: The John & Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Ruth
authors.initials: R
authors.lastname: McPherson
authors.affiliation: The John & Jennifer Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Roberts
authors.affiliation: deCODE Genetics and University of Iceland, Faculty of Medicine, 101, Reykjavik, Iceland.
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: Institut für Epidemiologie II, Helmholtz Zentrum München, Neuherberg, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.affiliation: Institut für Epidemiologie II, Helmholtz Zentrum München, Neuherberg, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.affiliation: Institut für Epidemiologie II, Helmholtz Zentrum München, Neuherberg, Germany; Munich Heart Alliance, Munich, Germany.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Rawal
authors.affiliation: Department of Health Sciences, University of Leicester, Leicester, UK.
authors.forename: John R
authors.initials: JR
authors.lastname: Thompson
authors.affiliation: Institut für Medizinische Biometrie und Statistik, Universität zu Lübeck, Lübeck, Germany.
authors.forename: Inke R
authors.initials: IR
authors.lastname: König
authors.affiliation: School of Medicine, Section of Preventive Medicine and Epidemiology, Boston University, Boston, MA, USA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.affiliation: Institut für Integrative und Experimentelle Genomik Universität zu Lübeck, DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Lübeck, Germany.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Erdmann
authors.affiliation: Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK; Leicester National Institute for Health Research Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, LE3 9QP, UK.
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.affiliation: Deutsches Herzzentrum and DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Technische Universität München, Munich, Germany.
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
mesh_terms: D016022:Case-Control Studies; D015897:Comorbidity; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D030541:Databases, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005060:Europe / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009656:North America / Q000453:epidemiology; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors
keywords: Cardiovascular disease; Coronary artery disease; Genome-wide association; SNP; Type-2 diabetes