Translational vision science & technology · 2026
Mitochondria-Related Gene BDH1 Implicated in Myopia Risk via Methylation-Regulated Expression: An Integrative Summary-Data Mendelian Randomization Study.
СтатьяНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Peng Shiming, Deng Hongwei, Tao Zhengyang, Chen Jing, Kang Zefeng
Аннотация
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.
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.