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Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus

Title: Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus
Author: Van Zuydam, Natalie R.
Ladenvall, Claes
Voight, Benjamin F.
Strawbridge, Rona J.
Fernandez-Tajes, Juan
Rayner, N. William
Robertson, Neil R.
Mahajan, Anubha
Vlachopoulou, Efthymia
Goel, Anuj
... 40 more authors Show all authors
Date: 2020-12-01
Language: English
Scope: E002769
School: Health Sciences
Series: Circulation: Genomic and Precision Medicine; 13(6)
ISSN: 1942-325X
DOI: https://doi.org/10.1161/CIRCGEN.119.002769
Subject: blood pressure; coronary artery disease; diabetes mellitus; genome-wide association study; risk factors; Genetics; Cardiology and Cardiovascular Medicine; Genetics (clinical)
URI: https://hdl.handle.net/20.500.11815/4032

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Van Zuydam , N R , Ladenvall , C , Voight , B F , Strawbridge , R J , Fernandez-Tajes , J , Rayner , N W , Robertson , N R , Mahajan , A , Vlachopoulou , E , Goel , A , Kleber , M E , Nelson , C P , Kwee , L C , Esko , T , Mihailov , E , Mägi , R , Milani , L , Fischer , K , Kanoni , S , Kumar , J , Song , C , Hartiala , J A , Pedersen , N L , Perola , M , Gieger , C , Peters , A , Qu , L , Willems , S M , Doney , A S F , Morris , A D , Zheng , Y , Sesti , G , Hu , F B , Qi , L , Laakso , M , Thorsteinsdottir , U , Grallert , H , Van Duijn , C , Reilly , M P , Ingelsson , E , Deloukas , P , Kathiresan , S , Metspalu , A , Shah , S H , Sinisalo , J , Salomaa , V , Hamsten , A , Samani , N J , März , W & Hazen , S L 2020 , ' Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus ' , Circulation: Genomic and Precision Medicine , vol. 13 , no. 6 , pp. E002769 . https://doi.org/10.1161/CIRCGEN.119.002769


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.


This work was supported by the European Union Framework Programme 7 (FP7/2007-2013) for the Innovative Medicine Initiative (IMI) under grant agreement n° IMI/115006 (the SUMMIT [Surrogate Markers for Micro- and Macro-Vascular Hard End Points for Innovative Diabetes Tools] consortium); Aarno Koskelo Foundation; Academy of Finland (no. 263401; no. 2676882); American Heart Association (13SDG14330006); AstraZeneca; AtheroSysMed (Systems medicine of coronary heart disease and stroke); British Heart Foundation Centre of Research Excellence at Oxford; ERC269045-Gene Target T2D grant; Estonian Research Council (IUT20-60, PUT1660 and PUT1665P); Estonian Center of Genomics/Roadmap II (project No. 2014-2020.4.01.16-0125); European Union (no. 692145; no. 633589; no. 313010; LSHM-CT-2007-037273; no. 201668; 2014-2020.4.01.15-0012;QLG1-CT-2002-00896; EU/QLRT-2001-01254; QLG2-CT-2002-01254 HEALTH-F2-2013-601456); Finnish Foundation for Cardiovascular research; Gentransmed - Centre of Excellence for Genomics and Translational Medicine; German Ministry of Education and Research (no. 01ZX1313A-K); Helsinki University Central Hospital special government funds (TYH7215, TKK2012005, TYH2012209, TYH2014312); Juvenile Diabetes Research Foundation (JDRF, 2-SRA-2014-276-Q-R); National Institute of Diabetes and Digestive and Kidney diseases (NIDDK, 5R01DK106236; U01-DK066134; U01-DK105535; R01DK101478); National Heart, Lung and Blood Institute (NLHBI, R01HL103866); National Institute for Health Research (NIHR); Personalized diagnostics and treatment of high risk coronary artery disease patients (RiskyCAD; 305739); Sigrid Juselius Foundation; Finnish Academy (no. 269517); Finnish Foundation for Cardiovascular Research; Foundation for Strategic Research and Stockholm County Council (560283; 592229); Juho Vainio Foundation; Knut and Alice Wallenberg Foundation; Ministry for Higher Education; Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council; Swedish Foundation for Strategic Research (SSF; ICA08-0047); Swedish Heart-Lung Foundation; Swedish Research Council (project 8691; 2015-02558; 2016-00598; M-2005-1112 and 2009-2298); Torsten and Ragnar Söderberg Foundation; W.W. Smith Charitable Trust (H1201); Wellcome Trust Institutional strategic support fund; Yrjö Jahnsson Foundation. Publisher Copyright: © 2020 Lippincott Williams and Wilkins. All rights reserved.

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