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. 2024 Nov 13;16(1):157.
doi: 10.1186/s13148-024-01772-1.

DNA methylation biomarkers and myopia: a multi-omics study integrating GWAS, mQTL and eQTL data

Xing-Xuan Dong  1 , Dong-Ling Chen  1 , Hui-Min Chen  1 , Dan-Lin Li  1 , Dan-Ning Hu  2 , Carla Lanca  3   4 , Andrzej Grzybowski  5 , Chen-Wei Pan  6
Affiliations

DNA methylation biomarkers and myopia: a multi-omics study integrating GWAS, mQTL and eQTL data

Xing-Xuan Dong et al. Clin Epigenetics. .

Abstract

Background: This study aimed to identify DNA methylation biomarkers associated with myopia using summary-data-based Mendelian randomization (SMR).

Methods: 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.

Results: 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).

Conclusions: 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.

Keywords: Biomarker; DNA methylation; Mendelian randomization; Multi-omics; Myopia.

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Conflict of interest statement

Declarations Ethics approval and consent to participate Given that this study represents a reevaluation of previously collected and published data, no additional ethical approval or informed consent from the subjects was needed. Competing interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overview of summary-data-based Mendelian randomization analyses of eQTL, mQTL, and GWAS datasets. Note SNP: single nucleotide polymorphism; GWAS: genome-wide association study; mQTL: methylation quantitative trait locus; eQTL: expression quantitative trait locus; SMR: summary-data-based Mendelian randomization; HEIDI: heterogeneity in dependent instruments
Fig. 2
Fig. 2
Results of summary data-based Mendelian randomization. Shown are -log10 (P values) from the summary-data-based Mendelian randomization (SMR) tests for AF against the physical positions of DNA methylation (left) or gene expression probes (right). The red lines represent the significance thresholds of the SMR tests
Fig. 3
Fig. 3
Identified genes associated with refractive error of three-step summary data-based Mendelian randomization
See this image and copyright information in PMC

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