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Mitochondria-Related Gene BDH1 Implicated in Myopia Risk via Methylation-Regulated Expression: An Integrative Summary-Data Mendelian Randomization Study

Year: 2026

Type: article

Abstract: Purpose: The purpose of this study was to prioritize mitochondria-related causal genes (MRGs) involved in myopia by integrating MRGs-related methylation quantitative trait loci (mQTL), expression quantitative trait loci (eQTL), and protein quantitative trait loci (pQTL) data with myopia genome-wide association study (GWAS) data. Methods: UK Biobank data were utilized for discovery, and FinnGen data for validation. Summary Data-based Mendelian Randomization (SMR) assessed associations between blood-derived MRG-related QTLs and myopia risk, followed by colocalization analysis to evaluate shared genetic etiology. Multi-omics integration linked methylation, expression, and disease risk. Results: Our integrative SMR analysis of MRGs prioritized BDH1 as the sole robust candidate. We identified a significant association between increased methylation at a promoter-proximal site (cg02569554) and reduced BDH1 expression (odds ratio [OR] = 0.522, 95% confidence interval [CI] = 0.425-0.641, false discovery rate [FDR] = 8.79 × 10⁻⁹). Although other nominal associations were observed, they did not survive multiple testing correction and are thus considered exploratory. Conclusions: This study provides integrative genetic evidence that BDH1 may contribute to myopia through methylation-regulated expression. However, the findings remain preliminary due to limited cross-layer consistency and require replication and functional validation. Translational Relevance: This study prioritizes BDH1 as a mitochondria-related gene that may influence myopia risk via methylation and expression changes, providing a candidate target for mechanistic research and therapeutic intervention.

Source: Translational Vision Science & Technology

DOI: 10.1167/tvst.15.1.7

Authors: Shiming Peng, Hongwei Deng, Zhengyang Tao, Jing Chen, Zefeng Kang

Institutions: Jinan University, Southern Medical University Shenzhen Hospital, Southern Medical University, China Academy of Chinese Medical Sciences

Language: English

Topic: Ophthalmology and Visual Impairment Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,850