title: A Mendelian randomization study of the effect of type-2 diabetes on coronary heart disease.
abstract: In observational studies, type-2 diabetes (T2D) is associated with an increased risk of coronary heart disease (CHD), yet interventional trials have shown no clear effect of glucose-lowering on CHD. Confounding may have therefore influenced these observational estimates. Here we use Mendelian randomization to obtain unconfounded estimates of the influence of T2D and fasting glucose (FG) on CHD risk. Using multiple genetic variants associated with T2D and FG, we find that risk of T2D increases CHD risk (odds ratio (OR)=1.11 (1.05-1.17), per unit increase in odds of T2D, P=8.8 × 10(-5); using data from 34,840/114,981 T2D cases/controls and 63,746/130,681 CHD cases/controls). FG in non-diabetic individuals tends to increase CHD risk (OR=1.15 (1.00-1.32), per mmol·per l, P=0.05; 133,010 non-diabetic individuals and 63,746/130,681 CHD cases/controls). These findings provide evidence supporting a causal relationship between T2D and CHD and suggest that long-term trials may be required to discern the effects of T2D therapies on CHD risk.
authors.affiliation: 1] Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec H3A 0G4, Canada [2] Department of Medicine, McGill University, Montreal, Quebec H3A 0G4, Canada.
authors.forename: Omar S
authors.initials: OS
authors.lastname: Ahmad
authors.affiliation: 1] Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec H3A 0G4, Canada [2] Department of Human Genetics, McGill University, Montréal, Québec H3A 0G4, Canada.
authors.forename: John A
authors.initials: JA
authors.lastname: Morris
authors.affiliation: 1] Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec H3A 0G4, Canada [2] Department of Medicine, McGill University, Montreal, Quebec H3A 0G4, Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Mujammami
authors.affiliation: 1] Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec H3A 0G4, Canada [2] Department of Medicine, McGill University, Montreal, Quebec H3A 0G4, Canada.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Forgetta
authors.affiliation: Division of General Internal Medicine, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Leong
authors.affiliation: 1] Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec H3A 0G4, Canada [2] Department of Medicine, McGill University, Montreal, Quebec H3A 0G4, Canada [3] Department of Human Genetics, McGill University, Montréal, Québec H3A 0G4, Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Oncology, Epidemiology, Biostatistics and Occupational Health, and Human Genetics, McGill University, Montreal, Quebec H3A 0G4, Canada.
authors.forename: Maxime
authors.initials: M
authors.lastname: Turgeon
authors.affiliation: Department of Oncology, Epidemiology, Biostatistics and Occupational Health, and Human Genetics, McGill University, Montreal, Quebec H3A 0G4, Canada.
authors.forename: Celia M T
authors.initials: CM
authors.lastname: Greenwood
authors.affiliation: 1] Department of Medicine, McGill University, Montreal, Quebec H3A 0G4, Canada [2] Department of Human Genetics, McGill University, Montréal, Québec H3A 0G4, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Thanassoulis
authors.affiliation: Division of General Internal Medicine, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Meigs
authors.affiliation: 1] Department of Medicine, McGill University, Montreal, Quebec H3A 0G4, Canada [2] Department of Human Genetics, McGill University, Montréal, Québec H3A 0G4, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Sladek
authors.affiliation: 1] Centre for Clinical Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec H3A 0G4, Canada [2] Department of Medicine, McGill University, Montreal, Quebec H3A 0G4, Canada [3] Department of Human Genetics, McGill University, Montréal, Québec H3A 0G4, Canada [4] Department of Twin Research and Genetic Epidemiology, King's College London, London SE1 7EH, UK.
authors.forename: J Brent
authors.initials: JB
authors.lastname: Richards
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D015984:Causality; D003327:Coronary Disease / Q000453:epidemiology / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000235:genetics / Q000378:metabolism; D006801:Humans; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human