Mendelian Randomization Suggests a Causal Link Between Glycemic Traits and Thoracic Aortic Structures and Diseases
We investigate the relationship between glycemic traits-specifically type 2 diabetes mellitus, fasting glucose, fasting insulin, glycated hemoglobin, and 2-hour post-load glucose-and thoracic aortic morphology and diseases. The results indicate an inverse association between elevated glycemic traits and aortic morphology, as well as a reduced risk of thoracic aortic aneurysm. Genetic predictors related to beta-cell proinsulin mechanisms in type 2 diabetes mellitus drive these associations. Key genes such as AGER, GLRX, TCF7L2, and GCK are implicated, highlighting their potential as therapeutic targets for the prevention and treatment of thoracic aortic aneurysm, given their role in glycemic control medication.
Authors
- W Rayner
- Alicia Huerta‐Chagoya (ORCID: https://orcid.org/0000-0001-6218-3904)
- James P. Pirruccello (ORCID: https://orcid.org/0000-0001-6088-4037)
- Justin Basile Echouffo-Tcheugui (ORCID: https://orcid.org/0000-0002-8460-1617)
- Hasan Alkhairo
- Xianyong Yin (ORCID: https://orcid.org/0000-0001-6454-2384)
- Pik Fang Kho (ORCID: https://orcid.org/0000-0001-7831-6062)
- Catherine Tcheandjieu (ORCID: https://orcid.org/0000-0001-9559-4339)
- James R. Priest (ORCID: https://orcid.org/0000-0002-8349-4784)
- Konstantinos Hatzikotoulas (ORCID: https://orcid.org/0000-0002-4699-3672)
- Derek Klarin (ORCID: https://orcid.org/0000-0002-4636-5780)
- Henry J. Taylor (ORCID: https://orcid.org/0000-0003-2088-5240)
- Lorraine Southam
- Philip S. Tsao (ORCID: https://orcid.org/0000-0001-7274-9318)
- Ken Suzuki (ORCID: https://orcid.org/0000-0003-1065-3593)
- Kruthika Iyer (ORCID: https://orcid.org/0000-0002-1247-7418)
- Michael G. Levin (ORCID: https://orcid.org/0000-0002-9937-9932)
- Scott M. Damrauer (ORCID: https://orcid.org/0000-0001-8009-1632)
- Ravi Mandla (ORCID: https://orcid.org/0000-0002-0782-0138)
- Tselmen Daria
Institutions
- Broad Institute (US)
- Gladstone Institutes (US)
- Johns Hopkins University (US)
- University of California, San Francisco (US)
- VA Palo Alto Health Care System (US)
- Johns Hopkins Medicine (US)
- Helmholtz Zentrum München (DE)
- National Institute for Health and Care Research (GB)
- Massachusetts General Hospital (US)
- NTT (United States) (US)
- Arthritis UK (GB)
- Philadelphia VA Medical Center (US)
- Nanjing Medical University (CN)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2025-10-31
- DOI
- https://doi.org/10.1016/j.jacbts.2025.101390
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00