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Lu Y, Dimitrov L, Chen SH, et al. Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes. Circ Genom Precis Med. 2021;14(4):e003258doi: 10.1161/CIRCGEN.120.003258.
Lu, Y., Dimitrov, L., Chen, S. H., Bielak, L. F., Bis, J. C., Feitosa, M. F., Lu, L., Kavousi, M., Raffield, L. M., Smith, A. V., Wang, L., Weiss, S., Yao, J., Zhu, J., Gudmundsson, E. F., Gudmundsdottir, V., Bos, D., Ghanbari, M., Ikram, M. A., Hwang, S. J., Taylor, K. D., Budoff, M. J., Gíslason, G. K., O'Donnell, C. J., An, P., Franceschini, N., Freedman, B. I., Fu, Y. P., Guo, X., Heiss, G., Kardia, S. L. R., Wilson, J. G., Langefeld, C. D., Schminke, U., Uitterlinden, A. G., Lange, L. A., Peyser, P. A., Gudnason, V. G., Psaty, B. M., Rotter, J. I., Bowden, D. W., & Ng, M. C. Y. (2021). Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes. Circulation. Genomic and precision medicine, 14(4), e003258. https://doi.org/10.1161/CIRCGEN.120.003258
Lu, Yingchang, et al. "Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes." Circulation. Genomic and precision medicine vol. 14,4 (2021): e003258. doi: https://doi.org/10.1161/CIRCGEN.120.003258
Lu Y, Dimitrov L, Chen SH, Bielak LF, Bis JC, Feitosa MF, Lu L, Kavousi M, Raffield LM, Smith AV, Wang L, Weiss S, Yao J, Zhu J, Gudmundsson EF, Gudmundsdottir V, Bos D, Ghanbari M, Ikram MA, Hwang SJ, Taylor KD, Budoff MJ, Gíslason GK, O'Donnell CJ, An P, Franceschini N, Freedman BI, Fu YP, Guo X, Heiss G, Kardia SLR, Wilson JG, Langefeld CD, Schminke U, Uitterlinden AG, Lange LA, Peyser PA, Gudnason VG, Psaty BM, Rotter JI, Bowden DW, Ng MCY. Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes. Circ Genom Precis Med. 2021 Aug;14(4):e003258. doi: 10.1161/CIRCGEN.120.003258. Epub 2021 Jul 09. PMID: 34241534; PMCID: PMC8435075.
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Circ Genom Precis Med. 2021 Aug;14(4):e003258. doi: 10.1161/CIRCGEN.120.003258. Epub 2021 Jul 09.

Multiethnic Genome-Wide Association Study of Subclinical Atherosclerosis in Individuals With Type 2 Diabetes.

Circulation. Genomic and precision medicine

Yingchang Lu, Latchezar Dimitrov, Shyh-Huei Chen, Lawrence F Bielak, Joshua C Bis, Mary F Feitosa, Lingyi Lu, Maryam Kavousi, Laura M Raffield, Albert V Smith, Lihua Wang, Stefan Weiss, Jie Yao, Jiaxi Zhu, Elias F Gudmundsson, Valborg Gudmundsdottir, Daniel Bos, Mohsen Ghanbari, M Arfan Ikram, Shih-Jen Hwang, Kent D Taylor, Matthew J Budoff, Gauti K Gíslason, Christopher J O'Donnell, Ping An, Nora Franceschini, Barry I Freedman, Yi-Ping Fu, Xiuqing Guo, Gerardo Heiss, Sharon L R Kardia, James G Wilson, Carl D Langefeld, Ulf Schminke, André G Uitterlinden, Leslie A Lange, Patricia A Peyser, Vilmundur G Gudnason, Bruce M Psaty, Jerome I Rotter, Donald W Bowden, Maggie C Y Ng

Affiliations

  1. Division of Genetic Medicine, Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN (Y.L., M.C.Y.N.).
  2. Center for Precision Medicine (L.D., C.D.L., D.W.B., M.C.Y.N.), Wake Forest School of Medicine, Winston-Salem, NC.
  3. Department of Biostatistics and Data Science (S.-H.C., L.L., C.D.L.), Wake Forest School of Medicine, Winston-Salem, NC.
  4. Department of Epidemiology (L.F.B., S.L.R.K., P.A.P.).
  5. Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services (J.C.B.), University of Washington, Seattle.
  6. Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine, Farrell Learning Center, St Louis, MO (M.F.F., L.W., J.Z., P.A.).
  7. Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands (M.K., D.B., M.G., M.A.I., A.G.U.).
  8. Department of Genetics (L.M.R.), University of North Carolina, Chapel Hill.
  9. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI (A.V.S.).
  10. Faculty of Medicine, University of Iceland, Reykjavik (A.V.S., E.F.G., V.G., G.K.G., V.G.G.).
  11. Icelandic Heart Association, Kopavogur (A.V.S., E.F.G., V.G., G.K.G., V.G.G.).
  12. Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University of Greifswald and University Medicine Greifswald, Germany (S.W.).
  13. DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Germany (S.W.).
  14. Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA (J.Y., K.D.T., X.G., J.I.R.).
  15. Department of Radiology and Nuclear Medicine (D.B.).
  16. The Population Sciences Branch, Division of Intramural Research (S.-J.H), National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
  17. The Framingham Heart Study, National Heart, Lung and Blood Institute, National Institutes of Health, Framingham, MA (S.-J.H., Y.-P.F.).
  18. Division of Cardiology, Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA (M.J.B.).
  19. VA Boston Healthcare System (C.J.O.), Harvard Medical School, Boston, MA.
  20. Department of Medicine, Brigham Women's Hospital (C.J.O.), Harvard Medical School, Boston, MA.
  21. Department of Medicine (C.J.O.), Harvard Medical School, Boston, MA.
  22. Department of Epidemiology (N.F., G.H.), University of North Carolina, Chapel Hill.
  23. Department of Internal Medicine (B.I.F.), Wake Forest School of Medicine, Winston-Salem, NC.
  24. Office of Biostatistics Research (Y.-P.F.), National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
  25. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.).
  26. Department of Cardiology, Beth Israel Deaconess Medical Center, Boston, MA (J.G.W.).
  27. Department of Neurology, University Medicine Greifswald, Germany (U.S.).
  28. Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands (A.G.U.).
  29. Division of Biomedical Informatics and Personalized Medicine, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora (L.A.L.).
  30. Departments of Epidemiology and Health Services (B.M.P.), University of Washington, Seattle.
  31. Department of Biochemistry (D.W.B.), Wake Forest School of Medicine, Winston-Salem, NC.

PMID: 34241534 PMCID: PMC8435075 DOI: 10.1161/CIRCGEN.120.003258

Abstract

BACKGROUND: Coronary artery calcification (CAC) and carotid artery intima-media thickness (cIMT) are measures of subclinical atherosclerosis in asymptomatic individuals and strong risk factors for cardiovascular disease. Type 2 diabetes (T2D) is an independent cardiovascular disease risk factor that accelerates atherosclerosis.

METHODS: We performed meta-analyses of genome-wide association studies in up to 2500 T2D individuals of European ancestry (EA) and 1590 T2D individuals of African ancestry with or without exclusion of prevalent cardiovascular disease, for CAC measured by cardiac computed tomography, and 3608 individuals of EA and 838 individuals of African ancestry with T2D for cIMT measured by ultrasonography within the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium.

RESULTS: We replicated 2 loci (rs9369640 and rs9349379 near

CONCLUSIONS: Our results provide potential biological mechanisms that could link CAC and cIMT to increased cardiovascular disease risk in individuals with T2D.

Keywords: atherosclerosis; carotid intima-media thickness; coronary artery disease; genetics; genome-wide association study

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