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Kiel, Christina ; Strunz, Tobias ; Grassmann, Felix ; Weber, Bernhard H. F.

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

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftCells
Verlag:MDPI
Ort der Veröffentlichung:BASEL
Band:9
Nummer des Zeitschriftenheftes oder des Kapitels:10
Seitenbereich:S. 2257
Datum2020
InstitutionenMedizin > Lehrstuhl für Humangenetik
Identifikationsnummer
WertTyp
10.3390/cells9102257DOI
Stichwörter / KeywordsGENOME-WIDE ASSOCIATION; GENE-EXPRESSION; HYPERTENSION; DISEASE; ATLAS; BLOOD; age-related macular degeneration; choroidal neovascularization; pleiotropy; miRNA variant; eQTL; locus analysis; gender specificity
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenZum Teil
URN der UB Regensburgurn:nbn:de:bvb:355-epub-440905
Dokumenten-ID44090

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