Skip to content
DraconiticResearch
Search Sources API
197,768 studies31 sourcesUpdated 8 min ago
Peer-reviewedCC BY-NC-ND 4.0Investigative Ophthalmology & Visual Science

Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma: A Multidimensional Genome-Wide Analysis

  • Zuyi Yang1
  • Dianzhe Tian2
  • Erqian Wang1
  • Xinyu Zhao1
  • Lei Zhang2
  • Yiyao Xu2
  • Xin Lu2
  • Youxin Chen1
  1. 1Department of Ophthalmology, Key Lab of Ocular Fundus Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  2. 2Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Read full textDOICite

Abstract

Purpose: Observational studies have suggested a positive association between myopia and primary open-angle glaucoma (POAG), yet the genetic mechanisms underlying their comorbidity remain incompletely understood. This study aimed to systematically characterize the shared genetic architecture between myopia and POAG using a multidimensional analytical framework.

Methods: We conducted an integrative genetic analysis using large-scale European ancestry genome-wide association study (GWAS) summary statistics for myopia (65,574 cases; 333,242 controls) and POAG (16,677 cases; 199,580 controls). Global and local genetic correlations were estimated using linkage disequilibrium score regression (LDSC), Genetic Covariance Analyzer, and SUPERGNOVA. Polygenic overlap was quantified using a bivariate causal mixture model (MiXeR). Shared loci were identified through conjunctional false discovery rate (conjFDR) analyses. Transcriptome-wide association studies, Multi-marker Analysis of GenoMic Annotation, and Polygenic Priority Score were applied for shared gene prioritization. Spatial enrichment was evaluated using genetically informed spatial mapping of cells for complex traits (gsMap).

Results: Myopia and POAG showed a significant positive genetic correlation (LDSC rg = 0.16, P = 1.09 × 10−5). MiXeR revealed substantial polygenic overlap, with 403 shared trait-influencing variants (Dice coefficient = 0.47), of which 71.9% showed concordant effects. ConjFDR identified 31 shared loci, including a strong signal at the BICC1 locus. Gene-level analyses highlighted BICC1, TFAP2B, AFAP1, and LOXL1 as key shared candidate genes. Spatial mapping localized shared genetic enrichment to mesenchymal-derived embryonic tissues.

Conclusions: Myopia and POAG exhibit a significant genetic correlation, substantial polygenic overlap, and multiple shared susceptibility loci and genes. Their comorbidity is likely driven by convergent developmental and biomechanical pathways. These findings provide novel insights into the genetic basis of myopia–POAG comorbidity and may facilitate future mechanistic studies and risk stratification.

Related

  1. Shared genetic architecture between adhesive capsulitis and type 2 diabetes: a phenotype-specific cross-trait analysis
    Jialin Dong, Mingkuan Yang, Yuchen Zhang +6
    Scientific ReportsPeer-reviewedCC BY-NC-ND 4.0Genetics & genomicsCrossref
  2. Integrating multi-omics analysis reveals shared genetic architecture and spatial correlations between heart failure and osteoporosis
    Ruikang Liu, Chiyun Sun, Yonghao Li +14
    Scientific ReportsPeer-reviewedCC BY-NC-ND 4.0Full textGenetics & genomicsCrossref
  3. Cross trait analysis reveals shared genetic architecture of eight common female reproductive disorders
    Ziwei Xie, Hao Xiong, Yingying Lin +9
    Communications BiologyPeer-reviewedCC BY-NC-ND 4.0Full text1 citedGenetics & genomicsPMC
  4. Genomic structural equation modeling uncovers shared genetic architecture and comorbidity mechanisms of lung function decline
    Guanglei Chen, Yunzhi Chen, Cancan Chu +1
    Scientific ReportsPeer-reviewedCC BYFull textGenetics & genomicsDOAJ
  5. Identifying the shared genetic architecture among severe COVID-19, type 2 diabetes, and obesity using cross-trait meta-analysis
    Seunghwan Park, Jieun Seo, Taesung Park +1
    Scientific ReportsPeer-reviewedCC BYFull textGenetics & genomicsDOAJ

Cite

BibTeXRIS
BibTeX
@article{yang2026shared,
  title = {{Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma: A Multidimensional Genome-Wide Analysis}},
  author = {Zuyi Yang and Dianzhe Tian and Erqian Wang and Xinyu Zhao and Lei Zhang and Yiyao Xu and Xin Lu and Youxin Chen},
  journal = {Investigative Ophthalmology \& Visual Science},
  year = {2026},
  month = oct,
  doi = {10.1167/iovs.67.12.65},
  url = {https://doi.org/10.1167/iovs.67.12.65},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Shared Genetic Architecture Between Myopia and Primary Open-Angle Glaucoma: A Multidimensional Genome-Wide Analysis
AU  - Zuyi Yang
AU  - Dianzhe Tian
AU  - Erqian Wang
AU  - Xinyu Zhao
AU  - Lei Zhang
AU  - Yiyao Xu
AU  - Xin Lu
AU  - Youxin Chen
PY  - 2026
DA  - 2026/10/26
JO  - Investigative Ophthalmology & Visual Science
DO  - 10.1167/iovs.67.12.65
UR  - https://doi.org/10.1167/iovs.67.12.65
AB  - Purpose: Observational studies have suggested a positive association between myopia and primary open-angle glaucoma (POAG), yet the genetic mechanisms underlying their comorbidity remain incompletely understood. This study aimed to systematically characterize the shared genetic architecture between myopia and POAG using a multidimensional analytical framework.  Methods: We conducted an integrative genetic analysis using large-scale European ancestry genome-wide association study (GWAS) summary statistics for myopia (65,574 cases; 333,242 controls) and POAG (16,677 cases; 199,580 controls). Global and local genetic correlations were estimated using linkage disequilibrium score regression (LDSC), Genetic Covariance Analyzer, and SUPERGNOVA. Polygenic overlap was quantified using a bivariate causal mixture model (MiXeR). Shared loci were identified through conjunctional false discovery rate (conjFDR) analyses. Transcriptome-wide association studies, Multi-marker Analysis of GenoMic Annotation, and Polygenic Priority Score were applied for shared gene prioritization. Spatial enrichment was evaluated using genetically informed spatial mapping of cells for complex traits (gsMap).  Results: Myopia and POAG showed a significant positive genetic correlation (LDSC rg = 0.16, P = 1.09 × 10−5). MiXeR revealed substantial polygenic overlap, with 403 shared trait-influencing variants (Dice coefficient = 0.47), of which 71.9% showed concordant effects. ConjFDR identified 31 shared loci, including a strong signal at the BICC1 locus. Gene-level analyses highlighted BICC1, TFAP2B, AFAP1, and LOXL1 as key shared candidate genes. Spatial mapping localized shared genetic enrichment to mesenchymal-derived embryonic tissues.  Conclusions: Myopia and POAG exhibit a significant genetic correlation, substantial polygenic overlap, and multiple shared susceptibility loci and genes. Their comorbidity is likely driven by convergent developmental and biomechanical pathways. These findings provide novel insights into the genetic basis of myopia–POAG comorbidity and may facilitate future mechanistic studies and risk stratification.
SN  - 0146-0404
SN  - 1552-5783
ER  -