| Title: | Pleiotropic Locus 15q24.1 Reveals a Gender-Specific Association with Neovascular but Not Atrophic Age-Related Macular Degeneration (AMD) |
| Journal: | Cells |
| Published: | 8 Oct 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33050031/ |
| DOI: | https://doi.org/10.3390/cells9102257 |
| URL: | https://www.mdpi.com/2073-4409/9/10/2257/pdf |
Publication 9240
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Abstract
Genome-wide association studies (GWAS) have identified an abundance of genetic loci associated with complex traits and diseases. In contrast, in-depth characterization of an individual genetic signal is rarely available. Here, we focus on the genetic variant rs2168518 in 15q24.1 previously associated with age-related macular degeneration (AMD), but only with suggestive evidence. In a two-step procedure, we initially conducted a series of association analyses to further delineate the association of rs2168518 with AMD but also with other complex phenotypes by using large independent datasets from the International AMD Genomics Consortium (IAMDGC) and the UK Biobank. We then performed a functional annotation with reference to gene expression regulation based on data from the Genotype-Tissue Expression (GTEx) project and RegulomeDB. Association analysis revealed a gender-specific association with male AMD patients and an association predominantly with choroidal neovascularization. Further, the AMD association colocalizes with an association signal of several blood pressure-related phenotypes and with the gene expression regulation of CYP1A1, a member of the cytochrome P450 superfamily of monooxygenases. Functional annotation revealed altered transcription factor (TF) binding sites for gender-specific TFs, including SOX9 and SRY. In conclusion, the pleiotropic 15q24.1 association signal suggests a shared mechanism between blood pressure regulation and choroidal neovascularization with a potential involvement of CYP1A1.</p>
5 Authors
- Christina Kiel
- Tobias Strunz
- International Amd Genomics Consortium Project Manager Susan Blanton Iamdgc
- Felix Grassmann
- Bernhard H F Weber
1 Application
| Application ID | Title |
|---|---|
| 44862 | The genetic landscape of complex diseases/traits - Exploring genetic risk scores to identify shared genetics and functional pathways |
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