Transcriptome-wide Association Study Identifies Genetically Dysregulated Genes in Diabetic Neuropathy

Author(s): Danfeng Lan, Hong-Yan Jiang, Xiaoyang Su, Yan Zhao, Sicheng Du, Ying Li, Rui Bi, Deng-Feng Zhang*, Qiuping Yang*

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 24 , Issue 2 , 2021


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Abstract:

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.

Keywords: Diabetic neuropathy, genome-wide association study, transcriptome-wide association study, differential expression, expression quantitative trait loci, diabetes mellitus.

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Article Details

VOLUME: 24
ISSUE: 2
Year: 2021
Published on: 08 August, 2020
Page: [319 - 325]
Pages: 7
DOI: 10.2174/1386207323666200808173745
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