| Title: | Genome-wide analysis of genetic pleiotropy and causal genes across three age-related ocular disorders |
| Journal: | Human Genetics |
| Published: | 14 Mar 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36917350/ |
| DOI: | https://doi.org/10.1007/s00439-023-02542-4 |
Publication 11198
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Abstract
Age-related macular degeneration (AMD), cataract, and glaucoma are leading causes of blindness worldwide. Previous genome-wide association studies (GWASs) have revealed a variety of susceptible loci associated with age-related ocular disorders, yet the genetic pleiotropy and causal genes across these diseases remain poorly understood. By leveraging large-scale genetic and observational data from ocular disease GWASs and UK Biobank (UKBB), we found significant pairwise genetic correlations and consistent epidemiological associations among these ocular disorders. Cross-disease meta-analysis uncovered seven pleiotropic loci, three of which were replicated in an additional cohort. Integration of variants in pleiotropic loci and multiple single-cell omics data identified that Müller cells and astrocytes were likely trait-related cell types underlying ocular comorbidity. In addition, we comprehensively integrated eye-specific gene expression quantitative loci (eQTLs), epigenomic profiling, and 3D genome data to prioritize causal pleiotropic genes. We found that pleiotropic genes were essential in nerve development and eye pigmentation, and targetable by aflibercept and pilocarpine for the treatment of AMD and glaucoma. These findings will not only facilitate the mechanistic research of ocular comorbidities but also benefit the therapeutic optimization of age-related ocular diseases.</p>
12 Authors
- Xueming Yao
- Hongxi Yang
- Han Han
- Xuejing Kou
- Yuhan Jiang
- Menghan Luo
- Yao Zhou
- Jianhua Wang
- Xutong Fan
- Xiaohong Wang
- Mulin Jun Li
- Hua Yan
1 Application
| Application ID | Title |
|---|---|
| 83974 | A framework for analyzing associations and interactions of genetic and non-genetic risk factors toward complex disease outcomes |
Enabling scientific discoveries that improve human health