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

## TL;DR

This study investigates whether diabetes and activin A levels are causally linked using genetic data, finding no evidence of a causal relationship.

## Contribution

The paper provides new insights into the lack of causal link between diabetes and plasma activin A levels using Mendelian randomization.

## Key findings

- Mendelian randomization analysis found no causal link between diabetes and plasma activin A levels.
- Multiple MR methods (IVW, Egger, etc.) consistently showed no association.
- Strong genetic instruments for activin A are lacking, preventing reverse analysis.

## Abstract

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.