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.

Graphical Abstract

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This article contains supplementary material online at https://doi.org/10.2337/figshare.25444327.

© 2024 by the American Diabetes Association
2024
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