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Genetic Risk Score ...
Genetic Risk Score Analysis Supports a Joint View of Two Classification Systems for Age-Related Macular Degeneration
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Herold, Janina M. (author)
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Zimmermann, Martina E. (author)
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Gorski, Mathias (author)
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- Günther, Felix, 1992- (author)
- Stockholms universitet,Matematiska institutionen
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Weber, Bernhard H. F. (author)
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Helbig, Horst (author)
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Stark, Klaus J. (author)
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Heid, Iris M. (author)
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Brandl, Caroline (author)
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(creator_code:org_t)
- 2023
- 2023
- English.
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In: Investigative Ophthalmology and Visual Science. - 0146-0404 .- 1552-5783. ; 64:12
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
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- 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 Universität 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Annan medicin och hälsovetenskap -- Gerontologi, medicinsk/hälsovetenskaplig inriktning (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Other Medical and Health Sciences -- Gerontology, specialising in Medical and Health Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Oftalmologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Ophthalmology (hsv//eng)
Keyword
- 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)
Publication and Content Type
- ref (subject category)
- art (subject category)
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Herold, Janina M ...
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Zimmermann, Mart ...
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Gorski, Mathias
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Günther, Felix, ...
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Weber, Bernhard ...
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Helbig, Horst
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show more...
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Stark, Klaus J.
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Heid, Iris M.
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Brandl, Caroline
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Other Medical an ...
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MEDICAL AND HEAL ...
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and Health Sciences
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and Public Health Gl ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Ophthalmology
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Stockholm University