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

doi:10.2337/dc23-2274

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

Research output: Contribution to journal › Article › Academic › peer-review

3 Downloads (Pure)

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.

Original language	English
Article number	e38652672
Pages (from-to)	1042-1047
Number of pages	6
Journal	Diabetes Care
Volume	47
Issue number	6
Early online date	23 Apr 2024
DOIs	https://doi.org/10.2337/dc23-2274
Publication status	Published - 1 Jun 2024

Access to Document

10.2337/dc23-2274

dc232274Final published version, 14.9 MBLicence: Taverne

Cite this

@article{8aecd23a0082485fb2a30eed3e942bcb,

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

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 {\texttimes} 10-9), rs77142250 (near HS3ST1, HR 1.89, P = 9.9 {\texttimes} 10-9), and rs335407 (near TFB1M/NOX3, HR 1.25, P = 1.5 {\texttimes} 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 {\texttimes} 10-16). CONCLUSIONS The data point to novel and known genomic regions associated with incident CVD among individuals with T2D.",

author = "Kwak, \{Soo Heon\} and Hernandez-Cancela, \{Ryan B\} and DiCorpo, \{Daniel A\} and Condon, \{David E\} and Jordi Merino and Peitao Wu and Brody, \{Jennifer A\} and Jie Yao and Xiuqing Guo and Fariba Ahmadizar and Mariah Meyer and Murat Sincan and Mercader, \{Josep M\} and Sujin Lee and Jeffrey Haessler and Vy, \{Ha My T\} and Zhaotong Lin and Armstrong, \{Nicole D\} and Shaopeng Gu and Tsao, \{Noah L\} and Lange, \{Leslie A\} and Ningyuan Wang and Wiggins, \{Kerri L\} and Stella Trompet and Simin Liu and Loos, \{Ruth J F\} and Renae Judy and Schroeder, \{Philip H\} and Hasbani, \{Natalie R\} and Bos, \{Maxime M\} and Morrison, \{Alanna C\} and Jackson, \{Rebecca D\} and Reiner, \{Alexander P\} and Manson, \{JoAnn E\} and Chaudhary, \{Ninad S\} and Carmichael, \{Lynn K\} and Chen, \{Yii-Der Ida\} and Taylor, \{Kent D\} and Mohsen Ghanbari and \{van Meurs\}, Joyce and Pitsillides, \{Achilleas N\} and Psaty, \{Bruce M\} and Raymond Noordam and Ron Do and Park, \{Kyong Soo\} and Jukema, \{J Wouter\} and Maryam Kavousi and Adolfo Correa and Rich, \{Stephen S\} and Damrauer, \{Scott M\}",

note = "Publisher Copyright: {\textcopyright} 2024 by the American Diabetes Association.",

year = "2024",

month = jun,

day = "1",

doi = "10.2337/dc23-2274",

language = "English",

volume = "47",

pages = "1042--1047",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association Inc.",

number = "6",

}

TY - JOUR

T1 - Time-to-Event Genome-Wide Association Study for Incident Cardiovascular Disease in People With Type 2 Diabetes

AU - Kwak, Soo Heon

AU - Hernandez-Cancela, Ryan B

AU - DiCorpo, Daniel A

AU - Condon, David E

AU - Merino, Jordi

AU - Wu, Peitao

AU - Brody, Jennifer A

AU - Yao, Jie

AU - Guo, Xiuqing

AU - Ahmadizar, Fariba

AU - Meyer, Mariah

AU - Sincan, Murat

AU - Mercader, Josep M

AU - Lee, Sujin

AU - Haessler, Jeffrey

AU - Vy, Ha My T

AU - Lin, Zhaotong

AU - Armstrong, Nicole D

AU - Gu, Shaopeng

AU - Tsao, Noah L

AU - Lange, Leslie A

AU - Wang, Ningyuan

AU - Wiggins, Kerri L

AU - Trompet, Stella

AU - Liu, Simin

AU - Loos, Ruth J F

AU - Judy, Renae

AU - Schroeder, Philip H

AU - Hasbani, Natalie R

AU - Bos, Maxime M

AU - Morrison, Alanna C

AU - Jackson, Rebecca D

AU - Reiner, Alexander P

AU - Manson, JoAnn E

AU - Chaudhary, Ninad S

AU - Carmichael, Lynn K

AU - Chen, Yii-Der Ida

AU - Taylor, Kent D

AU - Ghanbari, Mohsen

AU - van Meurs, Joyce

AU - Pitsillides, Achilleas N

AU - Psaty, Bruce M

AU - Noordam, Raymond

AU - Do, Ron

AU - Park, Kyong Soo

AU - Jukema, J Wouter

AU - Kavousi, Maryam

AU - Correa, Adolfo

AU - Rich, Stephen S

AU - Damrauer, Scott M

PY - 2024/6/1

Y1 - 2024/6/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85194013093

U2 - 10.2337/dc23-2274

DO - 10.2337/dc23-2274

M3 - Article

C2 - 38652672

SN - 0149-5992

VL - 47

SP - 1042

EP - 1047

JO - Diabetes Care

JF - Diabetes Care

IS - 6

M1 - e38652672

ER -

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

Abstract

Access to Document

Other files and links

Fingerprint

Cite this