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Pleiotropic Locus 15q24.1 Reveals a Gender-Specific Association with Neovascular but Not Atrophic Age-Related Macular Degeneration (AMD)
Kiel, Christina
, Strunz, Tobias
, Grassmann, Felix
und Weber, Bernhard H. F.
(2020)
Pleiotropic Locus 15q24.1 Reveals a Gender-Specific Association with Neovascular but Not Atrophic Age-Related Macular Degeneration (AMD).
Cells 9 (10), S. 2257.
Veröffentlichungsdatum dieses Volltextes: 13 Jan 2021 12:39
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.44090
Zusammenfassung
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 ...
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.
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Details
| Dokumentenart | Artikel | ||||
| Titel eines Journals oder einer Zeitschrift | Cells | ||||
| Verlag: | MDPI | ||||
|---|---|---|---|---|---|
| Ort der Veröffentlichung: | BASEL | ||||
| Band: | 9 | ||||
| Nummer des Zeitschriftenheftes oder des Kapitels: | 10 | ||||
| Seitenbereich: | S. 2257 | ||||
| Datum | 2020 | ||||
| Institutionen | Medizin > Lehrstuhl für Humangenetik | ||||
| Identifikationsnummer |
| ||||
| Stichwörter / Keywords | GENOME-WIDE ASSOCIATION; GENE-EXPRESSION; HYPERTENSION; DISEASE; ATLAS; BLOOD; age-related macular degeneration; choroidal neovascularization; pleiotropy; miRNA variant; eQTL; locus analysis; gender specificity | ||||
| Dewey-Dezimal-Klassifikation | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin | ||||
| Status | Veröffentlicht | ||||
| Begutachtet | Ja, diese Version wurde begutachtet | ||||
| An der Universität Regensburg entstanden | Zum Teil | ||||
| URN der UB Regensburg | urn:nbn:de:bvb:355-epub-440905 | ||||
| Dokumenten-ID | 44090 |
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