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Transcriptome-wide Association Study Identifies Genetically Dysregulated Genes in Diabetic Neuropathy
Combinatorial Chemistry & High Throughput Screening ( IF 1.6 ) Pub Date : 2021-01-31 , DOI: 10.2174/1386207323666200808173745
Danfeng Lan 1 , Hong-Yan Jiang 2 , Xiaoyang Su 1 , Yan Zhao 1 , Sicheng Du 1 , Ying Li 1 , Rui Bi 3 , Deng-Feng Zhang 3 , Qiuping Yang 1
Affiliation  

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.



中文翻译:

全转录组关联研究确定糖尿病神经病变中的遗传失调基因

背景:并发症是糖尿病疾病负担的主要原因。决定糖尿病并发症发生和进展的基因仍有待确定。糖尿病神经病变是最常见和使人衰弱的并发症,主要影响腿部和足部的神经。在这项研究中,我们试图从可靠的大规模全基因组关联研究 (GWAS) 中鉴定糖尿病神经病变特异性基因。

方法:利用公开可用的数据,我们最初使用基于功能汇总的插补 (FUSION) 算法将 GWAS 信号转换为胫神经中的转录组谱。然后检查 FUSION 衍生基因以确定它们是否在糖尿病神经病变小鼠模型的坐骨神经中差异表达。在糖尿病患者的血液中探索了在坐骨神经中发现的失调基因。

结果:我们发现 452 个 FUSION 衍生基因中有 11 个受糖尿病 GWAS 基因座调控,并且在早期神经病变小鼠模型的坐骨神经中发生改变。在这 11 个基因中,可以在人类患者的血液中检测到 HSD17B4、DHX32、MERTK 和 SFXN4 的显着(P 值<0.05)表达改变。

结论:我们的分析确定了对坐骨神经有影响的基因,并提供了无创早期检测糖尿病神经病变的可能性。

更新日期:2021-02-11
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