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

TitleTime-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People With Type 2 Diabetes.
Publication TypeJournal Article
Year of Publication2024
AuthorsKwak, SHeon, Hernandez-Cancela, RB, DiCorpo, DA, Condon, DE, Merino, J, Wu, P, Brody, JA, Yao, J, Guo, X, Ahmadizar, F, Meyer, M, Sincan, M, Mercader, JM, Lee, S, Haessler, J, Vy, HMy T, Lin, Z, Armstrong, ND, Gu, S, Tsao, NL, Lange, LA, Wang, N, Wiggins, KL, Trompet, S, Liu, S, Loos, RJF, Judy, R, Schroeder, PH, Hasbani, NR, Bos, MM, Morrison, AC, Jackson, RD, Reiner, AP, Manson, JAE, Chaudhary, NS, Carmichael, LK, Chen, Y-DI, Taylor, KD, Ghanbari, M, van Meurs, J, Pitsillides, AN, Psaty, BM, Noordam, R, Do, R, Park, KSoo, J Jukema, W, Kavousi, M, Correa, A, Rich, SS, Damrauer, SM, Hajek, C, Cho, NH, Irvin, MR, Pankow, JS, Nadkarni, GN, Sladek, R, Goodarzi, MO, Florez, JC, Chasman, DI, Heckbert, SR, Kooperberg, C, Dupuis, J, Malhotra, R, de Vries, PS, Liu, C-T, Rotter, JI, Meigs, JB
Corporate/Institutional AuthorsCohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
JournalDiabetes Care
Date Published2024 Apr 23
ISSN1935-5548
Abstract<p><b>OBJECTIVE: </b>To identify genetic risk factors for incident cardiovascular disease (CVD) among people with type 2 diabetes (T2D).</p><p><b>RESEARCH DESIGN AND METHODS: </b>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.</p><p><b>RESULTS: </b>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), rs11444867 (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).</p><p><b>CONCLUSIONS: </b>The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.</p>
DOI10.2337/dc23-2274
Alternate JournalDiabetes Care
PubMed ID38652672
Grant ListP30-DK063491 / DK / NIDDK NIH HHS / United States
U01HG011723 / HG / NHGRI NIH HHS / United States
UL1TR001420 / TR / NCATS NIH HHS / United States
ePub date: 
24/04