Diabetes Care. 2024;47(6):1042-1047.
Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People With Type 2 Diabetes.
제1저자 곽수헌 · 교신저자 James B. Meigs
소속 (38)
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.
- Broad Metabolism Program and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.
- Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.
- Department of Biostatistics, Boston University School of Public Health, Boston, MA.
- Sanford Imagenetics, Sanford Health, Sioux Falls, SD.
- Department of Medicine, Harvard Medical School, Boston, MA.
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
- Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.
- Department of Pediatrics, Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center, Torrance, CA.
- Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
- Department of Data Science and Biostatistics, Julius Global Health, University Medical Center Utrecht, Utrecht, the Netherlands.
- Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO.
- Division of Vascular Surgery and Endovascular Therapy, Massachusetts General Hospital, Boston, MA.
- Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA.
- Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY.
- Department of Biostatistics, University of Minnesota, Minneapolis, MN.
- Department of Epidemiology, The University of Alabama at Birmingham, Birmingham, AL.
- Department of Internal Medicine, Sanford Health, Sioux Falls, SD.
- Corporal Michael J. Crescenz VA Medical Center and Department of Surgery, Perelman School of Medicine, Philadelphia, PA.
- Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
- Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
- Department of Epidemiology, Brown University, Providence, RI.
- Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX.
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Ohio State University, Columbus, OH.
- Department of Epidemiology, University of Washington, Seattle, WA.
- Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
- Department of Health Systems and Population Health, University of Washington, Seattle, WA.
- Netherlands Heart Institute, Utrecht, the Netherlands.
- Department of Medicine, University of Mississippi Medical Center, Jackson, MS.
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
- Department of Genetics, Perelman School of Medicine, Philadelphia, PA.
- Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea.
- Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN.
- Department of Medicine and Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
- Cardiovascular Research Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA.
- Department 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.
© 2024 by the American Diabetes Association.
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그 밖의 정보
- 출판 형태
- Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
- 저널
- Diabetes care · eISSN 1935-5548
- MeSH
- Humans · Diabetes Mellitus, Type 2* / genetics / epidemiology / complications · Genome-Wide Association Study* · Cardiovascular Diseases* / genetics / epidemiology · Female · Male · Middle Aged · Aged · Polymorphism, Single Nucleotide
- 연구비
- American Diabetes Association 1-19-ICTS-068 · WHI NIH HHS 75N92021D00005 · NHLBI NIH HHS U01 HL080295 · NHLBI NIH HHS R01 HL159514 · NHLBI NIH HHS HHSN268201800015I · NHLBI NIH HHS N01 HC095160 · NHLBI NIH HHS N01 HC085080 · NHLBI NIH HHS R01 HL103612 · NHLBI NIH HHS 75N92020D00002 · NHLBI NIH HHS 75N92021D00002 · NHLBI NIH HHS HHSN268201500003C · NHLBI NIH HHS HHSN268201800012C · NHLBI NIH HHS N01 HC095161 · NHLBI NIH HHS 75N92020D00005 · NHLBI NIH HHS N01 HC095168 · NHLBI NIH HHS R01 HL120393 · NHLBI NIH HHS HHSN268201500001C · NCATS NIH HHS UL1 TR001079 · NHLBI NIH HHS N02 HL064278 · NHLBI NIH HHS N01 HC095169 · NHLBI NIH HHS N01 HC085082 · NCATS NIH HHS UL1 TR001878 · NHLBI NIH HHS HHSN268201800014I · NHLBI NIH HHS R01 HL043851 · NHLBI NIH HHS U01 HL130114 · NHLBI NIH HHS HHSN268200800007C · NHLBI NIH HHS R01 HL085251 · NHLBI NIH HHS 75N92020D00001 · NHLBI NIH HHS N01 HC085083 · NHLBI NIH HHS N01 HC085086 · NIH HHS S10 OD028685 · NHLBI NIH HHS N01 HC095167 · NHLBI NIH HHS R01 HL087652 · NHLBI NIH HHS T32 HL007457 · NHLBI NIH HHS HHSN268201800014C · NHLBI NIH HHS N01 HC095159 · NIH HHS S10 OD026880 · NHLBI NIH HHS R01 HL136666 · NHLBI NIH HHS 75N92020D00003 · NHLBI NIH HHS R01 HL105756 · NHLBI NIH HHS 75N92021D00001 · NIDDK NIH HHS P30 DK063491 · NIDDK NIH HHS R01 DK109588 · NHLBI NIH HHS R01 HL146860 · NHGRI NIH HHS U01HG011723 · NHLBI NIH HHS HHSN268201200036C · NHLBI NIH HHS HHSN268201800001C · Korean Minstry of Science and ICT RS-2023-00262002 · NHLBI NIH HHS N01 HC025195 · NIMHD NIH HHS HHSN268201800013I · CSRD VA IK2 CX001780 · NIDDK NIH HHS P30-DK063491 · NHLBI NIH HHS N01 HC055222 · NINDS NIH HHS U01 NS041588 · NHLBI NIH HHS HHSN268201500001I · NHLBI NIH HHS HHSN268201800012I · WHI NIH HHS 75N92021D00003 · NHLBI NIH HHS N01 HC085079 · NHGRI NIH HHS U01 HG011723 · NCATS NIH HHS UL1 TR001420 · NHLBI NIH HHS 75N92020D00004 · NCATS NIH HHS UL1 TR004419 · NCATS NIH HHS UL1TR001420 · NCI NIH HHS UM1 CA182913 · NHLBI NIH HHS 75N92020D00007 · NIGMS NIH HHS T32 GM100842 · NHLBI NIH HHS N01 HC095163 · NHLBI NIH HHS HHSN268201800011C · NCI NIH HHS R01 CA047988 · NHLBI NIH HHS HHSN268201500003I · NHLBI NIH HHS 75N92021D00006 · NIH HHS S10 OD030463 · NHLBI NIH HHS R01 HL080467 · NHLBI NIH HHS 75N92019D00031 · NCATS NIH HHS UL1 TR000040 · NHLBI NIH HHS N01 HC095166 · NHLBI NIH HHS R01 HL151855 · NHLBI NIH HHS HHSN268201800010I · NIDDK NIH HHS UM1 DK078616 · NHLBI NIH HHS N01 HC095162 · NHLBI NIH HHS 75N92020D00006 · NIA NIH HHS R01 AG023629 · NCATS NIH HHS UL1 TR001881 · NHLBI NIH HHS HHSN268201800011I · NHLBI NIH HHS N01 HC095165 · NHLBI NIH HHS N01 HC095164 · NHLBI NIH HHS R01 HL142809 · WHI NIH HHS 75N92021D00004 · NHLBI NIH HHS N01 HC085081 · NIDDK NIH HHS R01 DK125403
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