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

Soo Heon Kwak, Ryan B. Hernandez-Cancela, Daniel A. DiCorpo, Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, David E. Condon, Jordi Merino, Peitao Wu, Jennifer A. Brody, Jie Yao, Xiuqing Guo, Fariba Ahmadizar, Mariah Meyer, Murat Sincan, Josep M. Mercader, Sujin Lee, Jeffrey Haessler, Ha My T. Vy, Zhaotong Lin, Nicole D. Armstrong, Shaopeng GuNoah L. Tsao, Leslie A. Lange, Ningyuan Wang, Kerri L. Wiggins, Stella Trompet, Simin Liu, Ruth J.F. Loos, Renae Judy, Philip H. Schroeder, Natalie R. Hasbani, Maxime M. Bos, Alanna C. Morrison, Rebecca D. Jackson, Alexander P. Reiner, Jo Ann E. Manson, Ninad S. Chaudhary, Lynn K. Carmichael, Yii Der Ida Chen, Kent D. Taylor, Mohsen Ghanbari, Joyce van Meurs, Achilleas N. Pitsillides, Bruce M. Psaty, Raymond Noordam, Ron Do, Kyong Soo Park, J. Wouter Jukema, Maryam Kavousi, Jose C. Florez, Josée Dupuis, Paul S. de Vries

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)1042-1047
Number of pages6
JournalDiabetes Care
Issue number6
Publication statusPublished - 1 Jun 2024

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© 2024 by the American Diabetes Association.


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