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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Translational and Clinical Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1414585
This article is part of the Research Topic Stem Cell and Translational Medicine Research in Endocrine Diseases View all 5 articles

Association and causality between diabetes and activin A: a two-sample Mendelian randomization study

Provisionally accepted
  • Chengdu Medical College, Chengdu, China

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

    Activin A, a cytokine belonging to the transforming growth factor-beta (TGF-β) superfamily, mediates a multifunctional signaling pathway that is essential for embryonic development, cell differentiation, metabolic regulation, and physiological equilibrium.Biomedical research using diabetes-based model organisms and cellular cultures reports evidence of different activin A levels between diabetic and control groups. Activin A is highly conserved across species and universally expressed among disparate tissues. A systematic review of published literatures on human populations reveals association of plasma activin A levels with diabetic patients in some (7) but not in others (5) of the studies.With summarized data from publicly available genome-wide association studies (GWASs), a two-sample Mendelian randomization (TSMR) analysis is conducted on the causality between the exposure and the outcome. Wald ratio estimates from single instruments are predominantly non-significant. In contrast to positive controls between diabetes and plasma cholesterol levels, inverse-variance-weighted (IVW), Egger, weighted median, and weighted mode MR methods all lead to no observed causal link between diabetes (type 1 and type 2) and plasma activin A levels. Unavailability of strong instruments prevents the reversal MR analysis of activin A on diabetes. In summary, further research is needed to confirm or deny the potential association between diabetes and plasma activin A, and to elucidate the temporal incidence of these traits in human populations. At this stage, no causality has been found between diabetes and plasma activin A based on TSMR analysis.

    Keywords: Mendelian randomization, diabetes, activin A, Genomwide association studies, causal inference

    Received: 09 Apr 2024; Accepted: 15 Jul 2024.

    Copyright: © 2024 Wang. 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: Mengqiao Wang, Chengdu Medical College, Chengdu, China

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