Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus.

Case-Control Studies Coronary Artery Disease / complications Diabetes Mellitus, Type 2 / complications Genetic Predisposition to Disease Genome-Wide Association Study Humans Meta-Analysis as Topic Polymorphism, Genetic Risk Factors
blood pressure coronary artery disease diabetes mellitus genome-wide association study risk factors

Journal

Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113

Informations de publication

Date de publication:
12 2020
Historique:
entrez: 15 12 2020
pubmed: 16 12 2020
medline: 27 10 2021
Statut: ppublish

Résumé

Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D). To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D). None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.

Sections du résumé

BACKGROUND
Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).
METHODS
To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).
RESULTS
None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.
CONCLUSIONS
This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.

Identifiants

DOI: 10.1161/CIRCGEN.119.002769 PMID: 33321069 PMC: PMC7748049
pubmed: 33321069
doi: 10.1161/CIRCGEN.119.002769
pmc: PMC7748049
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e002769

Subventions

Organisme : NHLBI NIH HHS
ID : R01 HL103866
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK101478
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK046200
Pays : United States
Organisme : British Heart Foundation
ID : RG/14/5/30893
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : U01 DK105535
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK066134
Pays : United States
Organisme : NIDDK NIH HHS
ID : R56 DK101478
Pays : United States
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : NIDDK NIH HHS
ID : R01 DK106236
Pays : United States
Organisme : Medical Research Council
ID : MC_PC_13040
Pays : United Kingdom

Investigateurs

John Danesh (J)
Jeanette Erdmann (J)
Dongfeng Gu (D)
Jaspal S Kooner (JS)
Robert Roberts (R)
Heribert Schunkert (H)
Themistocles L Assimes (TL)
Stefan Blankenberg (S)
Bernhard O Boehm (BO)
John C Chambers (JC)
Robert Clarke (R)
Rory Collins (R)
George Dedoussis (G)
Paul W Franks (PW)
G Kees Hovingh (GK)
Bong-Jo Kim (BJ)
Terho Lehtimäki (T)
Ruth McPherson (R)
Markku S Nieminen (MS)
Christopher O'Donnell (C)
Samuli Ripatti (S)
Manjinder S Sandhu (MS)
Stefan Schreiber (S)
Agneta Siegbahn (A)
Cristen J Willer (CJ)
Pierre A Zalloua (PA)
Michael Mark (M)
Timo Kanninen (T)
Barbara Thorand (B)
Giuseppe Remuzzi (G)
David Dunger (D)
Angela Shore (A)
Ulf Smith (U)
Per-Henrik Groop (PH)
Seppo Ylä-Herttuala (S)
Claudio Cobelli (C)
Riccardo Bellazzi (R)
Ele Ferrannini (E)
Carlo Patrono (C)
Pirjo Nuutila (P)
Paul McKeague (P)
Birgit Steckel-Hamann (B)
Li-Ming Gan (LM)
Everson Nogoceke (E)
Piero Tortoli (P)
Bernd Jablonka (B)
Mary-Julia Brosnan (MJ)

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Auteurs

Natalie R van Zuydam (NR)

Pat Macpherson Center for Pharmacogenetics & Pharmacogenomics, Cardiovascular & Diabetes Medicine (N.R.v.Z., C.N.A.P.), School of Medicine, University of Dundee.
Oxford Center for Diabetes, Endocrinology & Metabolism, Radcliffe Department of Medicine (N.R.v.Z., N.W.R., N.R.R., A. Mahajan, M.I.Mc), University of Oxford, United Kingdom.
Wellcome Center for Human Genetics (N.R.v.Z., J.F.T., N.W.R., N.R.R, A. Mahajan, A.G., H.W., A.P.M., M.I.Mc), University of Oxford, United Kingdom.

Claes Ladenvall (C)

Department of Clinical Sciences, Diabetes & Endocrinology, Lund University Diabetes Center, Malmö, Sweden (C.L., L.G.).

Benjamin F Voight (BF)

Department of Systems Pharmacology & Translational Therapeutics (B.F.V.).
Department of Genetics (B.F.V.).
Institute for Translational Medicine & Therapeutics (B.F.V.).

Rona J Strawbridge (RJ)

Cardiovascular Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden (R.J.S., A.H.).

Juan Fernandez-Tajes (J)

Wellcome Center for Human Genetics (N.R.v.Z., J.F.T., N.W.R., N.R.R, A. Mahajan, A.G., H.W., A.P.M., M.I.Mc), University of Oxford, United Kingdom.

N William Rayner (NW)

Oxford Center for Diabetes, Endocrinology & Metabolism, Radcliffe Department of Medicine (N.R.v.Z., N.W.R., N.R.R., A. Mahajan, M.I.Mc), University of Oxford, United Kingdom.
Wellcome Center for Human Genetics (N.R.v.Z., J.F.T., N.W.R., N.R.R, A. Mahajan, A.G., H.W., A.P.M., M.I.Mc), University of Oxford, United Kingdom.
Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom (N.W.R.).

Neil R Robertson (NR)

Oxford Center for Diabetes, Endocrinology & Metabolism, Radcliffe Department of Medicine (N.R.v.Z., N.W.R., N.R.R., A. Mahajan, M.I.Mc), University of Oxford, United Kingdom.
Wellcome Center for Human Genetics (N.R.v.Z., J.F.T., N.W.R., N.R.R, A. Mahajan, A.G., H.W., A.P.M., M.I.Mc), University of Oxford, United Kingdom.

Anubha Mahajan (A)

Oxford Center for Diabetes, Endocrinology & Metabolism, Radcliffe Department of Medicine (N.R.v.Z., N.W.R., N.R.R., A. Mahajan, M.I.Mc), University of Oxford, United Kingdom.
Wellcome Center for Human Genetics (N.R.v.Z., J.F.T., N.W.R., N.R.R, A. Mahajan, A.G., H.W., A.P.M., M.I.Mc), University of Oxford, United Kingdom.

Efthymia Vlachopoulou (E)

Transplantation Laboratory, Haartman Institute (E.V.), University of Helsinki, Helsinki, Finland.

Anuj Goel (A)

Wellcome Center for Human Genetics (N.R.v.Z., J.F.T., N.W.R., N.R.R, A. Mahajan, A.G., H.W., A.P.M., M.I.Mc), University of Oxford, United Kingdom.
Division of Cardiovascular Medicine (A.G., H.W.), University of Oxford, United Kingdom.

Marcus E Kleber (ME)

Christopher P Nelson (CP)

Department of Cardiovascular Sciences, University of Leicester (C.P.N., N.J.S.).
NIHR Leicester Biomedical Research Center, Glenfield Hospital, Leicester, United Kingdom (C.P.N., N.J.S.).

Lydia Coulter Kwee (LC)

Duke Molecular Physiology Institute, Duke University, Durham, NC (L.C.K., S.H.S.).

Tõnu Esko (T)

Estonian Genome Center (T.E., E.M., R.M., L.M., K.F., M.P., A. Metspalu), University of Tartu, Tartu, Estonia.

Evelin Mihailov (E)

Estonian Genome Center (T.E., E.M., R.M., L.M., K.F., M.P., A. Metspalu), University of Tartu, Tartu, Estonia.

Reedik Mägi (R)

Estonian Genome Center (T.E., E.M., R.M., L.M., K.F., M.P., A. Metspalu), University of Tartu, Tartu, Estonia.

Lili Milani (L)

Estonian Genome Center (T.E., E.M., R.M., L.M., K.F., M.P., A. Metspalu), University of Tartu, Tartu, Estonia.

Krista Fischer (K)

Estonian Genome Center (T.E., E.M., R.M., L.M., K.F., M.P., A. Metspalu), University of Tartu, Tartu, Estonia.

Stavroula Kanoni (S)

Center for Genomic Health (S.K.), Queen Mary University of London, London, United Kingdom.
William Harvey Research Institute, Barts & the London Medical School (S.K., P.D.), Queen Mary University of London, London, United Kingdom.
Broad Institute of MIT & Harvard, Cambridge (S.K.).
Cardiology Division, Center for Human Genetic Research (S.K.), Massachusetts General Hospital & Harvard Medical School, Boston, MA.
Cardiovascular Research Center (S.K.), Massachusetts General Hospital & Harvard Medical School, Boston, MA.

Jitender Kumar (J)

Department of Medical Sciences, Molecular Epidemiology & Science for Life Laboratory (J.K., C.S., E.I.).
Center for Computational Biology & Bioinformatics, Amity Institute of Biotechnology, Amity University Uttar Pradesh, Noida, India (J.K.).

Ci Song (C)

Department of Medical Sciences, Molecular Epidemiology & Science for Life Laboratory (J.K., C.S., E.I.).
Department of Immunology, Genetics and Pathology, Medical Genetics & Genomics, Uppsala University, Uppsala, Sweden (C.S.).
Framingham Heart Study (C.S.).
Population Sciences Branch, National Heart, Lung & Blood Institute, National Institute of Health, Framingham, MA (C.S.).

Jaana A Hartiala (JA)

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (J.A.H.).

Nancy L Pedersen (NL)

Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden (N.L.P.).

Markus Perola (M)

Research Program for Clinical & Molecular Metabolism, Faculty of Medicine (M.P.), University of Helsinki, Helsinki, Finland. Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Estonian Genome Center (T.E., E.M., R.M., L.M., K.F., M.P., A. Metspalu), University of Tartu, Tartu, Estonia.
National Institute for Health and Welfare, Helsinki, Finland (M.P., V.S.).

Christian Gieger (C)

German Center for Diabetes Research (DZD), München-Neuherberg (C.G., A.P., H.G.).
Clinical Cooperation Group Type 2 Diabetes (C.G., H.G.), Helmholtz Zentrum München, Neuherberg, Germany.
German Research Center for Environmental Health & Institute of Genetic Epidemiology (C.G., A.P.), Helmholtz Zentrum München, Neuherberg, Germany.

Annette Peters (A)

German Center for Diabetes Research (DZD), München-Neuherberg (C.G., A.P., H.G.).
German Research Center for Environmental Health & Institute of Genetic Epidemiology (C.G., A.P.), Helmholtz Zentrum München, Neuherberg, Germany.
DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (A.P.).

Liming Qu (L)

Cardiovascular Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (L.Q., M.P.R.).
Department of Nutrition (Y.Z., F.B.H., L.Q.).
Department of Epidemiology, School of Public Health & Tropical Medicine, Tulane University, New Orleans, LA (L.Q.).

Sara M Willems (SM)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands (S.M.W., C.v.D.).

Alex S F Doney (ASF)

Division of Molecular & Clinical Medicine (A.S.F.D.), School of Medicine, University of Dundee.

Andrew D Morris (AD)

The Usher Institute of Population Health Sciences & Informatics (A.D.M.), University of Edinburgh, Edinburgh, U.K.
Health Data Research UK, London, United Kingdom (A.D.M.).

Yan Zheng (Y)

Department of Nutrition (Y.Z., F.B.H., L.Q.).
Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China (Y.Z.).

Giorgio Sesti (G)

University "Magna Graecia" of Catanzaro, Italy (G.S.).

Frank B Hu (FB)

Department of Nutrition (Y.Z., F.B.H., L.Q.).
Department of Epidemiology, Harvard School of Public Health, Boston, MA (F.B.H.).
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, MA (F.B.H.).

Lu Qi (L)

Cardiovascular Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (L.Q., M.P.R.).
Department of Nutrition (Y.Z., F.B.H., L.Q.).
Department of Epidemiology, School of Public Health & Tropical Medicine, Tulane University, New Orleans, LA (L.Q.).

Markku Laakso (M)

Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland (M.L.).
Kuopio University Hospital, Finland (M.L.).

Unnur Thorsteinsdottir (U)

Faculty of Medicine, University of Iceland. deCODE Genetics, Reykjavik, Iceland (U.T.).

Harald Grallert (H)

German Center for Diabetes Research (DZD), München-Neuherberg (C.G., A.P., H.G.).
Clinical Cooperation Group Type 2 Diabetes (C.G., H.G.), Helmholtz Zentrum München, Neuherberg, Germany.
Research Unit of Molecular Epidemiology, Institute of Epidemiology (H.G.), Helmholtz Zentrum München, Neuherberg, Germany.
Clinical Cooperation Group Nutrigenomics & Type 2 Diabetes (H.G.), Helmholtz Zentrum München, Neuherberg, Germany.

Cornelia van Duijn (C)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands (S.M.W., C.v.D.).

Muredach P Reilly (MP)

Cardiovascular Institute, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA (L.Q., M.P.R.).

Erik Ingelsson (E)

Department of Medical Sciences, Molecular Epidemiology & Science for Life Laboratory (J.K., C.S., E.I.).
Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine (E.I.).
Stanford Cardiovascular Institute (E.I.).
Stanford Diabetes Research Center, Stanford University, Stanford, CA (E.I.).

Panos Deloukas (P)

William Harvey Research Institute, Barts & the London Medical School (S.K., P.D.), Queen Mary University of London, London, United Kingdom.
Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia (P.D.).

Sek Kathiresan (S)

Center for Genomic Health (S.K.), Queen Mary University of London, London, United Kingdom.
William Harvey Research Institute, Barts & the London Medical School (S.K., P.D.), Queen Mary University of London, London, United Kingdom.
Broad Institute of MIT & Harvard, Cambridge (S.K.).
Cardiology Division, Center for Human Genetic Research (S.K.), Massachusetts General Hospital & Harvard Medical School, Boston, MA.
Cardiovascular Research Center (S.K.), Massachusetts General Hospital & Harvard Medical School, Boston, MA.

Andres Metspalu (A)

Estonian Genome Center (T.E., E.M., R.M., L.M., K.F., M.P., A. Metspalu), University of Tartu, Tartu, Estonia.
Institute of Cell & Molecular Biology (A. Metspalu), University of Tartu, Tartu, Estonia.

Svati H Shah (SH)

Division of Cardiology, Department of Medicine, Duke University Medical Center (S.H.S.).
Duke Molecular Physiology Institute, Duke University, Durham, NC (L.C.K., S.H.S.).

Juha Sinisalo (J)

Heart & Lung Center, Helsinki University Hospital (J.S.) and Institute for Molecular Medicine Finland (FIMM), Helsinki University, Helsinki, Finland.

Veikko Salomaa (V)

National Institute for Health and Welfare, Helsinki, Finland (M.P., V.S.).

Anders Hamsten (A)

Cardiovascular Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden (R.J.S., A.H.).

Nilesh J Samani (NJ)

Department of Cardiovascular Sciences, University of Leicester (C.P.N., N.J.S.).
NIHR Leicester Biomedical Research Center, Glenfield Hospital, Leicester, United Kingdom (C.P.N., N.J.S.).

Winfried März (W)

Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany (W.M.).
Clinical Institute of Medical & Chemical Laboratory Diagnostics, Medical University of Graz, Austria (W.M.).

Stanley L Hazen (SL)

Lerner Research Institute, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH (S.L.H.).

Hugh Watkins (H)

Wellcome Center for Human Genetics (N.R.v.Z., J.F.T., N.W.R., N.R.R, A. Mahajan, A.G., H.W., A.P.M., M.I.Mc), University of Oxford, United Kingdom.
Division of Cardiovascular Medicine (A.G., H.W.), University of Oxford, United Kingdom.

Danish Saleheen (D)

Department of Biostatistics & Epidemiology, University of Pennsylvania, Philadelphia, PA (D.S.).
Center for Non-Communicable Diseases, Karachi, Pakistan (D.S.).

Andrew P Morris (AP)

Wellcome Center for Human Genetics (N.R.v.Z., J.F.T., N.W.R., N.R.R, A. Mahajan, A.G., H.W., A.P.M., M.I.Mc), University of Oxford, United Kingdom.
Department of Biostatistics, University of Liverpool, Liverpool, U.K. (A.P.M.).
Division of Musculoskeletal & Dermatological Sciences, University of Manchester, Manchester, U.K. (A.P.M.).

Helen M Colhoun (HM)

MRC Institute of Genetics & Molecular Medicine (H.M.C.), University of Edinburgh, Edinburgh, U.K.
Public Health, NHS Fife, Kirkcaldy, Fife, U.K. (H.M.C.).

Leif Groop (L)

Department of Clinical Sciences, Diabetes & Endocrinology, Lund University Diabetes Center, Malmö, Sweden (C.L., L.G.).

Mark I McCarthy (MI)

Oxford Center for Diabetes, Endocrinology & Metabolism, Radcliffe Department of Medicine (N.R.v.Z., N.W.R., N.R.R., A. Mahajan, M.I.Mc), University of Oxford, United Kingdom.
Wellcome Center for Human Genetics (N.R.v.Z., J.F.T., N.W.R., N.R.R, A. Mahajan, A.G., H.W., A.P.M., M.I.Mc), University of Oxford, United Kingdom.
Oxford NIHR Biomedical Research Center, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom (M.I.Mc).

Colin N A Palmer (CNA)

Pat Macpherson Center for Pharmacogenetics & Pharmacogenomics, Cardiovascular & Diabetes Medicine (N.R.v.Z., C.N.A.P.), School of Medicine, University of Dundee.

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Classifications MeSH

questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études cas-témoins › Genetic Predisposition to Coronary Artery...
questionsmedicales.fr › Maladies cardiovasculaires › Maladies vasculaires › Ischémie myocardique › Maladie coronarienne › Maladie des artères coronaires › Genetic Predisposition to Coronary Artery...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › Genetic Predisposition to Coronary Artery...
questionsmedicales.fr › Phénomènes génétiques › Génotype › Prédisposition génétique à une maladie › Genetic Predisposition to Coronary Artery...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Épidémiologie moléculaire › Étude d'association pangénomique › Genetic Predisposition to Coronary Artery...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Genetic Predisposition to Coronary Artery...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méta-analyse comme sujet › Genetic Predisposition to Coronary Artery...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Polymorphisme génétique › Genetic Predisposition to Coronary Artery...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Probabilité › Risque › Facteurs de risque › Genetic Predisposition to Coronary Artery...