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

Title: Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People With Type 2 Diabetes
Authors: Kwak, SH; 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, HMT; 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, JE; Chaudhary, NS; Carmichael, LK; Chen, YI; Taylor, KD; Ghanbari, M; van Meurs, J; Pitsillides, AN; Psaty, BM; Noordam, R; Do, R; Park, KS; Jukema, JW; 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, CT; Rotter, JI; Meigs, JB; Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
Contributors: 101273; Cho, NH
Publication Year: 2024
Subject Terms: Aged; Cardiovascular Diseases; Diabetes Mellitus; Type 2; Female; Genome-Wide Association Study; Humans; Male; Middle Aged; Polymorphism; Single Nucleotide
Description: 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.
Document Type: article in journal/newspaper
Language: English
Relation: J001495992; http://repository.ajou.ac.kr/handle/201003/32600; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116923
DOI: 10.2337/dc23-2274
Availability: http://repository.ajou.ac.kr/handle/201003/32600; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11116923; https://doi.org/10.2337/dc23-2274
Accession Number: edsbas.5CE8F37D
Database: BASE