Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People With Type 2 Diabetes

Author:

Kwak Soo Heon123ORCID,Hernandez-Cancela Ryan B.4,DiCorpo Daniel A.4,Condon David E.5,Merino Jordi2367,Wu Peitao4,Brody Jennifer A.8,Yao Jie9,Guo Xiuqing9,Ahmadizar Fariba1011ORCID,Meyer Mariah12,Sincan Murat4,Mercader Josep M.236ORCID,Lee Sujin13,Haessler Jeffrey14,Vy Ha My T.15,Lin Zhaotong16,Armstrong Nicole D.17,Gu Shaopeng18,Tsao Noah L.19,Lange Leslie A.12,Wang Ningyuan4,Wiggins Kerri L.8,Trompet Stella2021,Liu Simin22ORCID,Loos Ruth J.F.15,Judy Renae19,Schroeder Philip H.236,Hasbani Natalie R.23,Bos Maxime M.10,Morrison Alanna C.23,Jackson Rebecca D.24,Reiner Alexander P.1425,Manson JoAnn E.26,Chaudhary Ninad S.17,Carmichael Lynn K.18,Chen Yii-Der Ida9,Taylor Kent D.9,Ghanbari Mohsen10,van Meurs Joyce10,Pitsillides Achilleas N.4,Psaty Bruce M.82527,Noordam Raymond20ORCID,Do Ron15ORCID,Park Kyong Soo1ORCID,Jukema J. Wouter2128,Kavousi Maryam10ORCID,Correa Adolfo29,Rich Stephen S.30ORCID,Damrauer Scott M.1931,Hajek Catherine18,Cho Nam H.32,Irvin Marguerite R.17ORCID,Pankow James S.33,Nadkarni Girish N.15ORCID,Sladek Robert34,Goodarzi Mark O.35ORCID,Florez Jose C.236ORCID,Chasman Daniel I.26ORCID,Heckbert Susan R.825,Kooperberg Charles14,Dupuis Josée436,Malhotra Rajeev37,de Vries Paul S.23,Liu Ching-Ti4ORCID,Rotter Jerome I.9,Meigs James B.2638ORCID,

Affiliation:

1. 1Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

2. 2Broad Metabolism Program and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA

3. 3Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA

4. 4Department of Biostatistics, Boston University School of Public Health, Boston, MA

5. 5Sanford Imagenetics, Sanford Health, Sioux Falls, SD

6. 6Department of Medicine, Harvard Medical School, Boston, MA

7. 7Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark

8. 8Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA

9. 9Department of Pediatrics, Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA

10. 10Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands

11. 11Department of Data Science and Biostatistics, Julius Global Health, University Medical Center Utrecht, Utrecht, the Netherlands

12. 12Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO

13. 13Division of Vascular Surgery and Endovascular Therapy, Massachusetts General Hospital, Boston, MA

14. 14Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA

15. 15Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY

16. 16Department of Biostatistics, University of Minnesota, Minneapolis, MN

17. 17Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, AL

18. 18Department of Internal Medicine, Sanford Health, Sioux Falls, SD

19. 19Corporal Michael J. Crescenz VA Medical Center and Department of Surgery, Perelman School of Medicine, Philadelphia, PA

20. 20Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands

21. 21Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands

22. 22Department of Epidemiology, Brown University, Providence, RI

23. 23Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX

24. 24Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Ohio State University, Columbus, OH

25. 25Department of Epidemiology, University of Washington, Seattle, WA

26. 26Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA

27. 27Department of Health Systems and Population Health, University of Washington, Seattle, WA

28. 28Netherlands Heart Institute, Utrecht, the Netherlands

29. 29Department of Medicine, University of Mississippi Medical Center, Jackson, MS

30. 30Center for Public Health Genomics, University of Virginia, Charlottesville, VA

31. 31Department of Genetics, Perelman School of Medicine, Philadelphia, PA

32. 32Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea

33. 33Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN

34. 34Department of Medicine and Department of Human Genetics, McGill University, Montreal, Quebec, Canada

35. 35Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA

36. 36Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada

37. 37Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA

38. 38Department of General Internal Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA

Abstract

OBJECTIVE To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS We conducted a multiancestry time-to-event genome-wide association study for incident CVD among people with T2D. We also tested 204 known coronary artery disease (CAD) variants for association with incident CVD. RESULTS Among 49,230 participants with T2D, 8,956 had incident CVD events (event rate 18.2%). We identified three novel genetic loci for incident CVD: rs147138607 (near CACNA1E/ZNF648, hazard ratio [HR] 1.23, P = 3.6 × 10−9), rs77142250 (near HS3ST1, HR 1.89, P = 9.9 × 10−9), and rs335407 (near TFB1M/NOX3, HR 1.25, P = 1.5 × 10−8). Among 204 known CAD loci, 5 were associated with incident CVD in T2D (multiple comparison–adjusted P < 0.00024, 0.05/204). A standardized polygenic score of these 204 variants was associated with incident CVD with HR 1.14 (P = 1.0 × 10−16). CONCLUSIONS The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.

Funder

American Diabetes Association

Korean Minstry of Science and ICT

National Institute of Diabetes and Digestive and Kidney Diseases

National Human Genome Research Institute

National Center for Advancing Translational Sciences

Publisher

American Diabetes Association

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3