BACKGROUND: Type 2 diabetes mellitus (T2D) and cardiovascular disease share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes mellitus. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. METHODS AND RESULTS: In a cross-sectional analysis, including ≤9210 European Americans, 3773 African Americans, 1446 Hispanic Americans, and 773 Chinese Americans without known cardiovascular disease and enrolled in the Framingham Heart Study, Coronary Artery Risk Development in Young Adults, Multi-Ethnic Study of Atherosclerosis, and Genetic Epidemiology Network of Arteriopathy studies, we tested a 62 T2D-loci genetic risk score for association with measures of SCA, including coronary artery or abdominal aortic calcium score, common and internal carotid artery intima-media thickness, and ankle-brachial index. We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors-adjusted model (significance, P<0.01=0.05/5, number of traits analyzed). An inverse association with coronary artery calcium score in Multi-Ethnic Study of Atherosclerosis Europeans (fully-adjusted P=0.004) and with common carotid artery intima-media thickness in the Framingham Heart Study (P=0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with β-cell and insulin resistance genetic risk sub-scores in the Framingham Heart Study and in the Coronary Artery Risk Development in Young Adults. CONCLUSIONS: SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and cardiovascular disease risk loci.
BACKGROUND: Type 2 diabetes mellitus (T2D) and cardiovascular disease share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes mellitus. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. METHODS AND RESULTS: In a cross-sectional analysis, including ≤9210 European Americans, 3773 African Americans, 1446 Hispanic Americans, and 773 Chinese Americans without known cardiovascular disease and enrolled in the Framingham Heart Study, Coronary Artery Risk Development in Young Adults, Multi-Ethnic Study of Atherosclerosis, and Genetic Epidemiology Network of Arteriopathy studies, we tested a 62 T2D-loci genetic risk score for association with measures of SCA, including coronary artery or abdominal aortic calcium score, common and internal carotid artery intima-media thickness, and ankle-brachial index. We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors-adjusted model (significance, P<0.01=0.05/5, number of traits analyzed). An inverse association with coronary artery calcium score in Multi-Ethnic Study of Atherosclerosis Europeans (fully-adjusted P=0.004) and with common carotid artery intima-media thickness in the Framingham Heart Study (P=0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with β-cell and insulin resistance genetic risk sub-scores in the Framingham Heart Study and in the Coronary Artery Risk Development in Young Adults. CONCLUSIONS: SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and cardiovascular disease risk loci.
Authors: J Jeffrey Carr; Jennifer Clark Nelson; Nathan D Wong; Michael McNitt-Gray; Yadon Arad; David R Jacobs; Stephan Sidney; Diane E Bild; O Dale Williams; Robert C Detrano Journal: Radiology Date: 2005-01 Impact factor: 11.105
Authors: Soo Lim; Jaeyoung Hong; Ching-Ti Liu; Marie-France Hivert; Charles C White; Joanne M Murabito; Christopher J O'Donnell; Josée Dupuis; Jose C Florez; James B Meigs Journal: Atherosclerosis Date: 2013-04-22 Impact factor: 5.162
Authors: C Alex McMahan; Samuel S Gidding; Jorma S A Viikari; Markus Juonala; Mika Kähönen; Nina Hutri-Kähönen; Eero Jokinen; Leena Taittonen; Matti Pietikäinen; Henry C McGill; Olli T Raitakari Journal: Am J Cardiol Date: 2007-07-16 Impact factor: 2.778
Authors: Jason L Vassy; Marie-France Hivert; Bianca Porneala; Marco Dauriz; Jose C Florez; Josée Dupuis; David S Siscovick; Myriam Fornage; Laura J Rasmussen-Torvik; Claude Bouchard; James B Meigs Journal: Diabetes Date: 2014-02-11 Impact factor: 9.337
Authors: Jan Rozman; Birgit Rathkolb; Manuela A Oestereicher; Christine Schütt; Aakash Chavan Ravindranath; Stefanie Leuchtenberger; Sapna Sharma; Martin Kistler; Monja Willershäuser; Robert Brommage; Terrence F Meehan; Jeremy Mason; Hamed Haselimashhadi; Tertius Hough; Ann-Marie Mallon; Sara Wells; Luis Santos; Christopher J Lelliott; Jacqueline K White; Tania Sorg; Marie-France Champy; Lynette R Bower; Corey L Reynolds; Ann M Flenniken; Stephen A Murray; Lauryl M J Nutter; Karen L Svenson; David West; Glauco P Tocchini-Valentini; Arthur L Beaudet; Fatima Bosch; Robert B Braun; Michael S Dobbie; Xiang Gao; Yann Herault; Ala Moshiri; Bret A Moore; K C Kent Lloyd; Colin McKerlie; Hiroshi Masuya; Nobuhiko Tanaka; Paul Flicek; Helen E Parkinson; Radislav Sedlacek; Je Kyung Seong; Chi-Kuang Leo Wang; Mark Moore; Steve D Brown; Matthias H Tschöp; Wolfgang Wurst; Martin Klingenspor; Eckhard Wolf; Johannes Beckers; Fausto Machicao; Andreas Peter; Harald Staiger; Hans-Ulrich Häring; Harald Grallert; Monica Campillos; Holger Maier; Helmut Fuchs; Valerie Gailus-Durner; Thomas Werner; Martin Hrabe de Angelis Journal: Nat Commun Date: 2018-01-18 Impact factor: 17.694
Authors: John Molvin; Amra Jujic; Peter M Nilsson; Margret Leosdottir; Ulf Lindblad; Bledar Daka; Louise Bennet; Lennart Råstam; Valeriya Lyssenko; Martin Magnusson Journal: ESC Heart Fail Date: 2019-12-20