School of Public Health, The Fourth Affiliated Hospital of Soochow University, Suzhou Medical College of Soochow University, Suzhou, China.
New York Eye and Ear Infirmary of Mount Sinai, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.
Clin Epigenetics. 2024 Nov 13;16(1):157. doi: 10.1186/s13148-024-01772-1.
This study aimed to identify DNA methylation biomarkers associated with myopia using summary-data-based Mendelian randomization (SMR).
A systematic search of the PubMed, Web of Science, Cochrane Library, and Embase databases was conducted up to March 27, 2024. SMR analyses were performed to integrate genome-wide association study (GWAS) with methylation quantitative trait loci (mQTL) and expression quantitative trait loci (eQTL) studies. The heterogeneity in the dependent instrument (HEIDI) test was utilized to distinguish pleiotropic associations from linkage disequilibrium.
The systematic review identified 26 DNA methylation biomarkers in five studies, with no overlap observed among those identified by different studies. After integrating GWAS with multi-omics data of mQTL and eQTL, six genes were significantly associated with myopia: PRMT6 (cg00944433 and cg15468180), SH3YL1 (cg03299269, cg11361895, and cg13354988), ZKSCAN4 (cg01192291), GATS (cg17830204), NPAT (cg04826772), and UBE2I (cg03545757 and cg08025960).
We identified six methylation biomarkers associated with the risk of myopia that may be helpful to elucidate the etiology mechanisms of myopia. Further experimental validation studies are required to corroborate these findings.
本研究旨在使用基于汇总数据的孟德尔随机化（SMR）来鉴定与近视相关的 DNA 甲基化生物标志物。
系统检索了 PubMed、Web of Science、Cochrane Library 和 Embase 数据库，检索时间截至 2024 年 3 月 27 日。采用 SMR 分析整合了全基因组关联研究（GWAS）与甲基化定量性状基因座（mQTL）和表达定量性状基因座（eQTL）研究。利用依赖工具（HEIDI）检验来区分多效性关联与连锁不平衡。
系统综述共确定了 26 个与近视相关的 DNA 甲基化生物标志物，不同研究确定的生物标志物没有重叠。在将 GWAS 与 mQTL 和 eQTL 的多组学数据整合后，有六个基因与近视显著相关：PRMT6（cg00944433 和 cg15468180）、SH3YL1（cg03299269、cg11361895、和 cg13354988）、ZKSCAN4（cg01192291）、GATS（cg17830204）、NPAT（cg04826772）和 UBE2I（cg03545757 和 cg08025960）。
我们确定了六个与近视风险相关的甲基化生物标志物，这些生物标志物可能有助于阐明近视的发病机制。需要进一步的实验验证研究来证实这些发现。
