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Herold, Janina M. ; Zimmermann, Martina E. ; Gorski, Mathias ; Günther, Felix ; Weber, Bernhard H. F. ; Helbig, Horst ; Stark, Klaus J. ; Heid, Iris M. ; Brandl, Caroline

Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration

Herold, Janina M., Zimmermann, Martina E. , Gorski, Mathias , Günther, Felix , Weber, Bernhard H. F., Helbig, Horst, Stark, Klaus J., Heid, Iris M. und Brandl, Caroline (2023) Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration. Investigative Opthalmology & Visual Science 64 (12), S. 31.

Veröffentlichungsdatum dieses Volltextes: 20 Okt 2023 11:52
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.54880


Zusammenfassung

PURPOSE. The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD. METHODS. In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universitat Regensburg), ...

PURPOSE. The purpose of this study was to evaluate the utility of combining the Clinical Classification (CC) and the Three Continent age-related macular degeneration (AMD) Consortium Severity Scale (3CACSS) for classification of AMD. METHODS. In two independent cross-sectional datasets of our population-based AugUR study (Altersbezogene Untersuchungen zur Gesundheit der Universitat Regensburg), we graded AMD via color fundus images applying two established classification systems (CC and 3CACSS). We calculated the genetic risk score (GRS) across 50 previously identified variants for late AMD, its association via logistic regression, and area under the curve (AUC) for each AMD stage. RESULTS. We analyzed 2188 persons aged 70 to 95 years. When comparing the two classification systems, we found a distinct pattern: CC "age-related changes" and CC "early AMD" distinguished individuals with 3CACSS "no AMD"; 3CACSS "mild/moderate/severe early AMD" stages, and distinguished CC "intermediate AMD". This suggested a 7-step scale combining the 2 systems: (i) "no AMD", (ii) "age-related changes", (iii) "very early AMD", (i.e. CC "early"), (iv) "mild early AMD", (v) "moderate early AMD", (vi) "severe early AMD", and (vii) "late AMD". GRS association and diagnostic accuracy increased stepwise by increased AMD severity in the 7-step scale and by increased restriction of controls (e.g. for CC "no AMD without age-related changes": AUC = 55.1%, 95% confidence interval [CI] = 51.6, 58.6, AUC = 62.3%, 95% CI = 59.1, 65.6, AUC = 63.8%, 95% CI = 59.3, 68.3, AUC = 78.1%, 95% CI = 73.6, 82.5, AUC = 82.2%, 95% CI = 78.4, 86.0, and AUC = 79.2%, 95% CI = 75.4, 83.0). A stepwise increase was also observed by increased drusen size and area. CONCLUSIONS. The utility of a 7-step scale is supported by our clinical and GRS data. This harmonization and full data integration provides an immediate simplification over using either CC or 3CACSS and helps to sharpen the control group.



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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftInvestigative Opthalmology & Visual Science
Verlag:ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Ort der Veröffentlichung:ROCKVILLE
Band:64
Nummer des Zeitschriftenheftes oder des Kapitels:12
Seitenbereich:S. 31
Datum18 September 2023
InstitutionenMedizin > Institut für Epidemiologie und Präventivmedizin
Medizin > Institut für Epidemiologie und Präventivmedizin > Lehrstuhl für Genetische Epidemiologie
Identifikationsnummer
WertTyp
10.1167/iovs.64.12.31DOI
Stichwörter / KeywordsGENOME-WIDE ASSOCIATION; GENOTYPE IMPUTATION; SEVERITY SCALE; MACULOPATHY; DISEASE; age-related macular degeneration (AMD); population-based study; genetic risk score (GRS); drusen; classification systems; clinical classification (CC); three continent AMD consortium severity scale (3CACSS)
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-548809
Dokumenten-ID54880

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