Multiomics Integration Prioritizes ZFP36L1 as a Candidate Susceptibility Gene Associated With Inflammatory and
Ruiqing Dong1, Xiaoli Hui2, Chenwen Luo3
1Department of Endocrinology and Metabolism, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China, xjtu.edu.cn.
Journal of Diabetes Research
|June 19, 2026
Summary
ZFP36L1 is identified as a novel gene associated with diabetic retinopathy (DR) risk. Its expression in blood correlates with DR, suggesting a role in inflammation and angiogenesis.
Area of Science:
- Genomics and Ophthalmology
- Multiomics research
- Diabetic complications
Background:
- Diabetic retinopathy (DR) is a leading cause of blindness.
- Current therapies for DR are insufficient, necessitating new therapeutic targets.
- Understanding the genetic and molecular underpinnings of DR is crucial.
Purpose of the Study:
- To identify novel genetic risk factors for diabetic retinopathy (DR).
- To investigate the molecular mechanisms linking genetic factors to DR pathogenesis.
- To explore the role of ZFP36L1 in inflammation and angiogenesis in DR.
Main Methods:
- Integrated multiomics analysis including single-cell RNA sequencing of rat retinal tissues.
- Mendelian randomization (MR) using eQTL and DR GWAS data.
- RT-qPCR validation in human peripheral blood samples.
Main Results:
- Mendelian randomization identified ZFP36L1 as a novel DR risk gene (OR = 1.156, p = 0.002).
- ZFP36L1 expression was significantly upregulated in DR patient blood (p < 0.0001) and correlated with inflammatory markers (TNF-α, IL-6).
- Functional analyses suggested links between ZFP36L1 and NF-κB inflammatory and TGF-β angiogenic pathways, with an unexpected positive correlation with VEGF.
Conclusions:
- ZFP36L1 is a candidate DR susceptibility gene with genetically regulated expression linked to DR risk.
- Retinal and pathway analyses suggest ZFP36L1 involvement in DR-related inflammation and angiogenesis.
- Further studies are needed to elucidate ZFP36L1's direct role in retinal pathophysiology in human DR.
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