Genetically proxied inhibition of kidney function pathways and increased risk of type 2 diabetes in Africans: A Mendelian randomization study

Objective: To investigate the causal relationship between genetically predicted inhibition of specific kidney function drug targets and the risk of type 2 diabetes (T2D) in African populations using Mendelian randomization (MR).

Methods: We used MR, a genetic proxy approach, and utilized genome-wide association study data from African participants. This assessed the causal relationship between genetically predicted inhibition of specific pathways and T2D risk. The analysis was conducted using TwoSampleMR package implemented in R.

Results: We found that inhibiting the vascular endothelial growth factor A (VEGFA) and Ras homolog enriched in brain (RHEB) was significantly linked to T2D risk in Africans (OR 2.66, 95% CI 1.34–3.78, p = 0.0017 and OR 2.25, 95% CI 1.34–3.28, p = 0.0010, respectively). Conversely, there was no evidence that solute-like carrier family 22 member A2 or claudin-14 were associated with an increased risk of T2D (OR = 0.95, 95% CI 0.61–1.48; OR = 1.56, 95% CI 0.71–2.20, respectively).

Conclusions: Insight from this study could potentially mean that some of the drugs that are used for treatment of kidney diseases involving VEGFA and RHEB may potentially increase the risk of developing T2D among Africans. This highlights how it is critical to consider drug–drug interaction in kidney diseases in Africa.