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

Autor:	Kwak SH; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea.; Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA., Hernandez-Cancela RB; Department of Biostatistics, Boston University School of Public Health, Boston, MA., DiCorpo DA; Department of Biostatistics, Boston University School of Public Health, Boston, MA., Condon DE; Sanford Imagenetics, Sanford Health, Sioux Falls, SD., Merino J; Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.; 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., Wu P; Department of Biostatistics, Boston University School of Public Health, Boston, MA., Brody JA; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA., Yao J; Department of Pediatrics, Institute for Translational Genomics and Population Science, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA., Guo X; Department of Pediatrics, Institute for Translational Genomics and Population Science, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA., Ahmadizar F; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.; Department of Data Science and Biostatistics, Julius Global Health, University Medical Center Utrecht, Utrecht, the Netherlands., Meyer M; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO., Sincan M; Department of Biostatistics, Boston University School of Public Health, Boston, MA., Mercader JM; Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.; Department of Medicine, Harvard Medical School, Boston, MA., Lee S; Division of Vascular Surgery and Endovascular Therapy, Massachusetts General Hospital, Boston, MA., Haessler J; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA., Vy HMT; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY., Lin Z; Department of Biostatistics, University of Minnesota, Minneapolis, MN., Armstrong ND; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL., Gu S; Department of Internal Medicine, Sanford Health, Sioux Falls, SD., Tsao NL; Corporal Michael Crescenz VA Medical Center, and Department of Surgery, Perelman School of Medicine, Philadelphia, PA., Lange LA; Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, CO., Wang N; Department of Biostatistics, Boston University School of Public Health, Boston, MA., Wiggins KL; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA., Trompet S; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.; Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands., Liu S; Department of Epidemiology, Brown University, Providence, RI., Loos RJF; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY., Judy R; Corporal Michael Crescenz VA Medical Center, and Department of Surgery, Perelman School of Medicine, Philadelphia, PA., Schroeder PH; Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.; Department of Medicine, Harvard Medical School, Boston, MA., Hasbani NR; 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., Bos MM; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands., Morrison AC; 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., Jackson RD; Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Ohio State University, Columbus, OH., Reiner AP; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA.; Department of Epidemiology, University of Washington, Seattle, WA., Manson JE; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Chaudhary NS; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL., Carmichael LK; Department of Internal Medicine, Sanford Health, Sioux Falls, SD., Chen YI; Department of Pediatrics, Institute for Translational Genomics and Population Science, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA., Taylor KD; Department of Pediatrics, Institute for Translational Genomics and Population Science, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA., Ghanbari M; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands., van Meurs J; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands., Pitsillides AN; Department of Biostatistics, Boston University School of Public Health, Boston, MA., Psaty BM; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.; Department of Epidemiology, University of Washington, Seattle, WA.; Department of Health Systems and Population Health, University of Washington, Seattle, WA., Noordam R; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands., Do R; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY., Park KS; Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea., Jukema JW; Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.; The Netherlands Heart Institute, Utrecht, the Netherlands., Kavousi M; Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands., Correa A; Department of Medicine, University of Mississippi Medical Center, Jackson, MS., Rich SS; Center for Public Health Genomics, University of Virginia, Charlottesville, VA., Damrauer SM; Corporal Michael Crescenz VA Medical Center, and Department of Surgery, Perelman School of Medicine, Philadelphia, PA.; Department of Genetics, Perelman School of Medicine, Philadelphia, PA., Hajek C; Department of Internal Medicine, Sanford Health, Sioux Falls, SD., Cho NH; Department of Preventive Medicine, Ajou University School of Medicine, Suwon, Korea., Irvin MR; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL., Pankow JS; Department of Biostatistics, University of Minnesota, Minneapolis, MN., Nadkarni GN; Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY., Sladek R; Department of Medicine and Department of Human Genetics, McGill University, Montréal, QC, Canada., Goodarzi MO; Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Cedars-Sinai Medical Center., Florez JC; Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.; Department of Medicine, Harvard Medical School, Boston, MA., Chasman DI; Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA., Heckbert SR; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA.; Department of Epidemiology, University of Washington, Seattle, WA., Kooperberg C; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA., Dupuis J; Department of Biostatistics, Boston University School of Public Health, Boston, MA.; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada., Malhotra R; Cardiovascular Research Center, Cardiology Division of the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA., de Vries PS; 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., Liu CT; Department of Biostatistics, Boston University School of Public Health, Boston, MA., Rotter JI; Department of Pediatrics, Institute for Translational Genomics and Population Science, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA., Meigs JB; Programs in Metabolism and Medical & Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA.; Department of Medicine, Harvard Medical School, Boston, MA.; Department of General Internal Medicine, Harvard Medical School and Massachusetts General Hospital, Boston, MA.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Jul 28. Date of Electronic Publication: 2023 Jul 28.
DOI:	10.1101/2023.07.25.23293180
Abstrakt:	Background: Type 2 diabetes mellitus (T2D) confers a two- to three-fold increased risk of cardiovascular disease (CVD). However, the mechanisms underlying increased CVD risk among people with T2D are only partially understood. We hypothesized that a genetic association study among people with T2D at risk for developing incident cardiovascular complications could provide insights into molecular genetic aspects underlying CVD. Methods: From 16 studies of the Cohorts for Heart & Aging Research in Genomic Epidemiology (CHARGE) Consortium, we conducted a multi-ancestry time-to-event genome-wide association study (GWAS) for incident CVD among people with T2D using Cox proportional hazards models. Incident CVD was defined based on a composite of coronary artery disease (CAD), stroke, and cardiovascular death that occurred at least one year after the diagnosis of T2D. Cohort-level estimated effect sizes were combined using inverse variance weighted fixed effects meta-analysis. We also tested 204 known CAD variants for association with incident CVD among patients with T2D. Results: A total of 49,230 participants with T2D were included in the analyses (31,118 European ancestries and 18,112 non-European ancestries) which consisted of 8,956 incident CVD cases over a range of mean follow-up duration between 3.2 and 33.7 years (event rate 18.2%). We identified three novel, distinct genetic loci for incident CVD among individuals with T2D that reached the threshold for genome-wide significance ( P <5.0×10 -8 ): rs147138607 (intergenic variant between CACNA1E and ZNF648 ) with a hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.15 - 1.32, P =3.6×10 -9 , rs11444867 (intergenic variant near HS3ST1 ) with HR 1.89, 95% CI 1.52 - 2.35, P =9.9×10 -9 , and rs335407 (intergenic variant between TFB1M and NOX3 ) HR 1.25, 95% CI 1.16 - 1.35, P =1.5×10 -8 . Among 204 known CAD loci, 32 were associated with incident CVD in people with T2D with P <0.05, and 5 were significant after Bonferroni correction ( P <0.00024, 0.05/204). A polygenic score of these 204 variants was significantly associated with incident CVD with HR 1.14 (95% CI 1.12 - 1.16) per 1 standard deviation increase ( P =1.0×10 -16 ). Conclusions: The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.
Databáze:	MEDLINE
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