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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Cardiovascular Epidemiology and Prevention
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1382702
This article is part of the Research Topic Mendelian Randomization and Cardiovascular Diseases View all 12 articles

Genetic Predisposition to Type 2 Diabetes Mellitus and Aortic Dissection: A Mendelian Randomisation Study.

Provisionally accepted
Yaodong Sun Yaodong Sun 1Dongdong Du Dongdong Du 1*Jiantao Zhang Jiantao Zhang 1,2,3*Linlin Zhao Linlin Zhao 1*Bufan Zhang Bufan Zhang 1*Yi Zhang Yi Zhang 1*Tianxu Song Tianxu Song 1*Naishi Wu Naishi Wu 1*
  • 1 Tianjin Medical University General Hospital, Tianjin, China
  • 2 Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, Shanxi Province, China
  • 3 Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China

The final, formatted version of the article will be published soon.

    Background: This Mendelian randomization (MR) study aimed to explore the causal relationship between the genetic predisposition to type 2 diabetes mellitus (T2DM) and aortic dissection (AD), and to assess associations with genetically predicted glycemic traits. The study sought to verify the inverse relationship between T2DM and AD using a more robust and unbiased method, building on the observational studies previously established.The study employed a two-sample and multivariable MR approach to analyze genetic data from the DIAbetes Meta-ANalysis of Trans-Ethnic association studies (DIAMANTE) with 74,124 cases and 824,006 controls, and the Meta-Analyses of Glucose and Insulin-Related Traits Consortium (MAGIC) involving up to 196,991 individuals. For AD data, FinnGen Release 10 was used, including 967 cases and 381,977 controls. The research focused on three foundational MR assumptions and controlled for confounders like hypertension. Genetic instruments were selected for their genome-wide significance, and multiple MR methods and sensitivity analyses were conducted.The study revealed no significant effect of genetic predisposition to T2DM on the risk of AD. Even after adjusting for potential confounders, the results were consistent, indicating no causal relationship. Additionally, glycemic traits such as fasting glucose, fasting insulin, and HbA1c levels did not show a significant impact on AD susceptibility. The findings remained stable across various MR models and sensitivity analyses. In contrast, genetic liability to T2DM and glycemic traits showed a significant association with coronary artery disease (CAD), aligning with the established understanding.Contrary to previous observational studies, this study concludes that genetic predisposition to T2DM does not confer protection against AD. These findings underscore the imperative for further research, particularly in exploring the preventative potential of T2DM treatments against AD and to facilitate the development of novel therapeutic interventions.

    Keywords: diabetes, aortic dissection, Mendelian randomisation, Genome-Wide Association Study, Epidemiology

    Received: 29 Feb 2024; Accepted: 05 Jul 2024.

    Copyright: © 2024 Sun, Du, Zhang, Zhao, Zhang, Zhang, Song and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Dongdong Du, Tianjin Medical University General Hospital, Tianjin, China
    Jiantao Zhang, Tianjin Medical University General Hospital, Tianjin, China
    Linlin Zhao, Tianjin Medical University General Hospital, Tianjin, China
    Bufan Zhang, Tianjin Medical University General Hospital, Tianjin, China
    Yi Zhang, Tianjin Medical University General Hospital, Tianjin, China
    Tianxu Song, Tianjin Medical University General Hospital, Tianjin, China
    Naishi Wu, Tianjin Medical University General Hospital, Tianjin, China

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