Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus,Circulation: Genomic and Precision Medicine

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Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus
Circulation: Genomic and Precision Medicine ( IF 6.0 ) Pub Date : 2020-08-13 , DOI: 10.1161/circgen.119.002769
Natalie R van Zuydam _{1,

2,

3} , Claes Ladenvall ₄ , Benjamin F Voight _{5,

6,

7} , Rona J Strawbridge ₈ , Juan Fernandez-Tajes ₃ , N William Rayner _{2,

3,

9} , Neil R Robertson _{2,

3} , Anubha Mahajan _{2,

3} , Efthymia Vlachopoulou ₁₀ , Anuj Goel _{3,

11} , Marcus E Kleber , Christopher P Nelson _{12,

13} , Lydia Coulter Kwee ₁₄ , Tõnu Esko ₁₅ , Evelin Mihailov ₁₅ , Reedik Mägi ₁₅ , Lili Milani ₁₅ , Krista Fischer ₁₅ , Stavroula Kanoni _{16,

17,

18,

19,

20} , Jitender Kumar _{21,

22} , Ci Song _{21,

23,

24,

25} , Jaana A Hartiala ₂₆ , Nancy L Pedersen ₂₇ , Markus Perola _{15,

28,

29} , Christian Gieger _{30,

31,

32} , Annette Peters _{30,

32,

33} , Liming Qu _{34,

35,

36} , Sara M Willems ₃₇ , Alex S F Doney ₃₈ , Andrew D Morris _{39,

40} , Yan Zheng _{35,

41} , Giorgio Sesti ₄₂ , Frank B Hu _{35,

43,

44} , Lu Qi _{34,

35,

36} , Markku Laakso _{45,

46} , Unnur Thorsteinsdottir ₄₇ , Harald Grallert _{30,

31,

48,

49} , Cornelia van Duijn ₃₇ , Muredach P Reilly ₃₄ , Erik Ingelsson _{21,

50,

51,

52} , Panos Deloukas _{17,

53} , Sek Kathiresan _{16,

17,

18,

19,

20} , Andres Metspalu _{15,

54} , Svati H Shah _{14,

55} , Juha Sinisalo ₅₆ , Veikko Salomaa ₂₉ , Anders Hamsten ₈ , Nilesh J Samani _{12,

13} , Winfried März _{57,

58} , Stanley L Hazen ₅₉ , Hugh Watkins _{3,

11} , Danish Saleheen _{60,

61} , Andrew P Morris _{3,

62,

63} , Helen M Colhoun _{64,

65} , Leif Groop ₄ , Mark I McCarthy _{2,

3,

66} , Colin N A Palmer ₁ ,

Affiliation

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.
Department of Clinical Sciences, Diabetes & Endocrinology, Lund University Diabetes Center, Malmö, Sweden (C.L., L.G.).
Department of Systems Pharmacology & Translational Therapeutics (B.F.V.).
Department of Genetics (B.F.V.).
Institute for Translational Medicine & Therapeutics (B.F.V.).
Cardiovascular Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden (R.J.S., A.H.).
Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom (N.W.R.).
Transplantation Laboratory, Haartman Institute (E.V.), University of Helsinki, Helsinki, Finland.
Division of Cardiovascular Medicine (A.G., H.W.), University of Oxford, United Kingdom.
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.).
Duke Molecular Physiology Institute, Duke University, Durham, NC (L.C.K., S.H.S.).
Estonian Genome Center (T.E., E.M., R.M., L.M., K.F., M.P., A. Metspalu), University of Tartu, Tartu, Estonia.
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.
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.).
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.).
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA (J.A.H.).
Department of Medical Epidemiology & Biostatistics, Karolinska Institutet, Stockholm, Sweden (N.L.P.).
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.
National Institute for Health and Welfare, Helsinki, Finland (M.P., V.S.).
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.
DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany (A.P.).
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.).
Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands (S.M.W., C.v.D.).
Division of Molecular & Clinical Medicine (A.S.F.D.), School of Medicine, University of Dundee.
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.).
Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China (Y.Z.).
University "Magna Graecia" of Catanzaro, Italy (G.S.).
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.).
Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland (M.L.).
Kuopio University Hospital, Finland (M.L.).
Faculty of Medicine, University of Iceland. deCODE Genetics, Reykjavik, Iceland (U.T.).
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.
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.).
Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia (P.D.).
Institute of Cell & Molecular Biology (A. Metspalu), University of Tartu, Tartu, Estonia.
Division of Cardiology, Department of Medicine, Duke University Medical Center (S.H.S.).
Heart & Lung Center, Helsinki University Hospital (J.S.) and Institute for Molecular Medicine Finland (FIMM), Helsinki University, Helsinki, Finland.
Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany (W.M.).
Clinical Institute of Medical & Chemical Laboratory Diagnostics, Medical University of Graz, Austria (W.M.).
Lerner Research Institute, Heart & Vascular Institute, Cleveland Clinic, Cleveland, OH (S.L.H.).
Department of Biostatistics & Epidemiology, University of Pennsylvania, Philadelphia, PA (D.S.).
Center for Non-Communicable Diseases, Karachi, Pakistan (D.S.).
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.).
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.).
Oxford NIHR Biomedical Research Center, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford, United Kingdom (M.I.Mc).

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.

中文翻译：

2 型糖尿病患者罹患冠状动脉疾病的遗传倾向

背景：冠状动脉疾病 (CAD) 在 2 型糖尿病 (T2D) 患者中加速。方法：为了测试这是否反映了 T2D 患者 CAD 风险的不同遗传影响，我们对 CAD 和 CAD 之间的遗传重叠进行了系统评估。 66 643 名受试者患有 T2D（27 708 名患有 CAD，24 259 名患有 T2D）。在分层分析或相互作用证据中显示与 CAD 明显相关的变异在另外 117 787 名受试者中进行了评估（16 694 名受试者患有 CAD，11 537 名受试者患有 T2D）。结果：未发现先前表征的 CAD 基因座对 CAD 有特定影响在 T2D 个体中，全基因组相互作用分析没有发现可被视为 T2D 特异性的 CAD 新变异。当我们考虑 CAD 与其危险因素之间的总体遗传相关性时，我们发现 T2D 背景的这些关系没有显着差异。结论：本研究没有发现任何证据表明 CAD 的遗传结构在 T2D 患者与非 T2D 患者中存在差异。

更新日期：2020-08-13

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