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2 results on '"DiCorpo DA"'

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

Author

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, and Meigs JB

Subjects
Humans, Female, Male, Middle Aged, Aged, Polymorphism, Single Nucleotide, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 complications, Genome-Wide Association Study, Cardiovascular Diseases genetics, Cardiovascular Diseases epidemiology
Abstract

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., (© 2024 by the American Diabetes Association.)

Published
2024
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2. Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People with Type 2 Diabetes Mellitus.

Author

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, and Meigs JB

Abstract

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.

Published
2023
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