The study provides strong evidence linking T2D and PAD through Mendelian randomization and bioinformatics analysis, but a couple of aspects could use further clarification. While TCF7L2 is identified as a key gene, how do the authors account for potential confounding effects from other genetic or environmental factors? Were sensitivity analyses performed to test the stability of this association? Additionally, given the study’s reliance on publicly available datasets, were any dataset-specific biases or limitations considered?
The concerns about confounding factors in the Mendelian randomization analysis are important. While the study identifies TCF7L2 as a key gene linking T2D and PAD, additional clarification on how potential genetic and environmental confounders were addressed would strengthen the findings. If sensitivity analyses were conducted to test the stability of this association, discussing these results in more detail would provide greater confidence in the conclusions.
Regarding dataset-specific biases, publicly available datasets often come with limitations related to population diversity, data collection methods, or batch effects. A discussion on how these factors were accounted for, such as through data harmonization techniques or validation with independent cohorts, would further enhance the study’s robustness and applicability.