Genetics
Genome-wide meta-analysis of myopic macular neovascularisation finds the AMD-linked CETP locus rs12720922 also protects against this retinal disease (Ophthalmol Retina 2025)
Original title: Genome-wide Meta-analysis for Myopic Macular Neovascularization Identified a Novel Susceptibility Locus and Revealed a Shared Genetic Susceptibility with Age-Related Macular Degeneration
A genome-wide association meta-analysis of 2,783 highly myopic individuals (608 with myopic macular neovascularisation, mMNV, 2,175 controls) combined three independent GWAS datasets to search for mMNV susceptibility loci. The meta-analysis identified a novel locus, rs56257842 at TEX29-LINC02337 (odds ratio 0.62, P = 4.63 times ten to the minus 8), consistent across all three datasets. Testing known age-related macular degeneration (AMD) susceptibility loci against mMNV, the CETP variant rs12720922 showed a statistically significant association (odds ratio 0.52, P = 1.55 times ten to the minus 5), while a variant near ARMS2 showed only a marginal association. The authors interpret this as evidence of shared genetic susceptibility between mMNV and AMD, with the CETP finding a secondary result within a study whose primary discovery is the TEX29-LINC02337 locus.
Original abstract
Purpose: To identify the susceptibility loci for myopic macular neovascularization (mMNV) in patients with high myopia.
Design: A genome-wide association study (GWAS) meta-analysis (meta-GWAS).
Participants: We included 2783 highly myopic individuals, including 608 patients with mMNV and 2175 control participants without mMNV.
Methods: We performed a meta-analysis of 3 independent GWASs conducted according to the genotyping platform (Illumina Asian Screening Array [ASA] data set, Illumina Human610 BeadChip [610K] data set, and whole genome sequencing [WGS] data set), adjusted for age, sex, axial length, and the first to third principal components. We used DeltaSVM to evaluate the binding affinity of transcription factors (TFs) to DNA sequences around the susceptibility of single nucleotide polymorphisms (SNPs). In addition, we evaluated the contribution of previously reported age-related macular degeneration (AMD) susceptibility loci.
Main Outcome Measures: The association between SNPs and mMNV in patients with high myopia.
Results: The meta-GWAS identified rs56257842 at TEX29- LINC02337 as a novel susceptibility SNP for mMNV (odds ratio [OR]meta = 0.62, Pmeta = 4.63 × 10-8, I2 = 0.00), which was consistently associated with mMNV in all data sets (ORASA = 0.59, PASA = 1.71 × 10-4; OR610K = 0.63, P610K = 5.53 × 10-4; ORWGS = 0.66, PWGS = 4.38 × 10-2). Transcription factor-wide analysis showed that the TFs ZNF740 and EGR1 lost their binding affinity to this locus when rs56257842 had the C allele (alternative allele), and the WNT signaling-related TF ZBTB33 gained binding affinity when rs56257842 had the C allele. When we examined the associations of AMD susceptibility loci, rs12720922 at CETP showed a statistically significant association with mMNV (ORmeta = 0.52, Pmeta = 1.55 × 10-5), whereas rs61871745 near ARMS2 showed a marginal association (ORmeta = 1.25, Pmeta = 7.79 × 10-3).
Conclusions: Our study identified a novel locus associated with mMNV in high myopia. Subsequent analyses offered important insights into the molecular biology of mMNV, providing the potential therapeutic targets for mMNV. Furthermore, our findings imply shared genetic susceptibility between mMNV and AMD.
Financial Disclosure(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.