Background: Complications are the main cause of the disease burden of diabetes. Genes
determining the development and progression of diabetic complications remain to be identified. Diabetic
neuropathy is the most common and debilitating complication and mainly affects the nerves
of legs and feet. In this study, we attempted to identify diabetic neuropathy-specific genes from reliable
large-scale genome-wide association studies (GWASs) for diabetes perse.
Methods: Taking advantage of publicly available data, we initially converted the GWAS signals to
transcriptomic profiles in the tibial nerve using the functional summary-based imputation (FUSION)
algorithm. The FUSION-derived genes were then checked to determine whether they were
differentially expressed in the sciatic nerve of mouse models of diabetic neuropathy. The dysregulated
genes identified in the sciatic nerve were explored in the blood of patients with diabetes.
Results: We found that eleven out of 452 FUSION-derived genes were regulated by diabetes
GWAS loci and were altered in the sciatic nerve of mouse models with early-stage neuropathy.
Among the eleven genes, significant (P-value<0.05) expression alterations of HSD17B4, DHX32,
MERTK, and SFXN4 could be detected in the blood of human patients.
Conclusions: Our analyses identified genes with an effect in the sciatic nerve and provided the possibility
of noninvasive early detection of diabetic neuropathy.