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

Link: https://doi.org/10.1101/2023.07.25.23293180
Authors: Kwak, Soo Heon; Hernandez-Cancela, Ryan B; DiCorpo, Daniel A; Condon, David E; Merino, Jordi; Wu, Peitao; Brody, Jennifer A; Yao, Jie; Guo, Xiuqing; Ahmadizar, Fariba; Meyer, Mariah; Sincan, Murat; Mercader, Josep M; Lee, Sujin; Haessler, Jeffrey; Vy, Ha My T; Lin, Zhaotong; Armstrong, Nicole D; Gu, Shaopeng; Tsao, Noah L; Lange, Leslie A; Wang, Ningyuan; Wiggins, Kerri L; Trompet, Stella; Liu, Simin; Loos, Ruth J F; Judy, Renae; Schroeder, Philip H; Hasbani, Natalie R; Bos, Maxime M; Morrison, Alanna C; Jackson, Rebecca D; Reiner, Alexander P; Manson, JoAnn E; Chaudhary, Ninad S; Carmichael, Lynn K; Chen, Yii-Der Ida; Taylor, Kent D; Ghanbari, Mohsen; van Meurs, Joyce; Pitsillides, Achilleas N; Psaty, Bruce M; Noordam, Raymond; Do, Ron; Park, Kyong Soo; Jukema, J Wouter; Kavousi, Maryam; Correa, Adolfo; Rich, Stephen S; Damrauer, Scott M; Hajek, Catherine; Cho, Nam H; Irvin, Marguerite R; Pankow, James S; Nadkarni, Girish N; Sladek, Robert; Goodarzi, Mark O; Florez, Jose C; Chasman, Daniel I; Heckbert, Susan R; Kooperberg, Charles; Dupuis, Josée; Malhotra, Rajeev; de Vries, Paul S; Liu, Ching-Ti; Rotter, Jerome I; Meigs, James B

Abstract: 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. 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. The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.

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