Obesity-Related Genes Linked to Kidney, Eye, and Nerve Damage in Diabetes

Recent genome-wide research reveals that common obesity traits are not only associated with increased body weight but also share significant genetic links to diabetic complications affecting multiple organs. The study, published in Biomolecules and Biomedicine, maps shared DNA signals, tests causal relationships, and identifies pathways that could enable earlier screening and targeted treatments for organ damage in diabetes.

Diabetes is a chronic condition characterized by high blood glucose levels, which over time can severely injure small blood vessels. This damage can lead to kidney failure when the kidneys are affected, vision loss from retinopathy, and nerve impairment resulting in pain, numbness, and autonomic dysfunction. These complications often co-occur, raising the risk of mortality despite current treatment strategies that aim to reduce these risks.

The research team analyzed seven obesity-related traits—including body mass index (BMI), waist-to-hip ratio, LDL and HDL cholesterol, total cholesterol, and triglycerides—using large datasets from genome-wide association studies. They examined their genetic correlations with three major diabetic microvascular complications: kidney disease, retinopathy, and neuropathy. The analysis employed methods to identify shared genetic factors and estimate causal directions through Mendelian randomization and latent causal models.

Findings indicated widespread genetic overlap, with significant sharing across 15 out of 21 trait-complication pairs and localized sharing in 97 genomic regions. From an initial pool of over 37,000 candidate variants, the study pinpointed 828 key signals, with 52 loci showing high-confidence colocalization, suggesting shared mechanisms rather than coincidental proximity.

Particularly compelling was evidence of causal relationships from obesity traits like BMI to diabetic kidney disease, and from waist-to-hip measures to retinopathy and neuropathy. HDL cholesterol emerged as an influential factor in neuropathy within the causal model. One gene, RPS26, was repeatedly linked across tissues and is known to influence p53 signaling pathways involved in cellular stress responses and survival.

The implications of these results are profound; they provide a detailed genetic map that can help identify individuals with obesity at higher risk for microvascular complications. Furthermore, they uncover shared biological pathways related to insulin secretion, lipid metabolism, MAP kinase activity, and calcium transport—processes essential for energy regulation, inflammation control, and vascular function. These pathways present potential targets for drugs with effects across multiple affected organs.

The study emphasizes that integrating genetic data with traditional risk factors could improve early detection and preventive strategies. For example, individuals with high BMI and identified genetic susceptibility could benefit from intensified weight management, lipid control, and closer monitoring of kidney and eye health.

Nevertheless, certain limitations exist, including the predominance of European ancestry in the datasets and the need for further functional studies to verify causal genes and pathways. Future research aims to include diverse populations, incorporate transcriptomic and proteomic data, and test targeted interventions in cell and animal models to explore therapeutic potential.

Ultimately, the researchers advocate a comprehensive approach to prevent diabetic microvascular damage by addressing obesity early, monitoring vulnerable organs based on genetic risk, and developing cross-organ protective treatments. This strategy holds promise to delay or lessen the severity of kidney failure, vision loss, and nerve damage in individuals affected by diabetes.

source: https://medicalxpress.com/news/2025-09-obesity-genes-kidney-eye-nerve.html