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000271698 0247_ $$2ISSN$$a1460-2202
000271698 0247_ $$2doi$$a10.1080/02713683.2024.2388692
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000271698 041__ $$aEnglish
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000271698 1001_ $$0P:(DE-2719)9002126$$aGarzone, David$$b0$$eFirst author
000271698 245__ $$aAge-Related Macular Degeneration and Its Genetic Risk: A Population-based Study.
000271698 260__ $$aAbingdon$$bTaylor & Francis Group$$c2025
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000271698 520__ $$aSpecific genetic factors might serve as markers for risk stratification of AMD progression, but their association with key features of AMD has not been fully elucidated. Thus, we investigated the association between overall and pathway-specific genetic risk scores (GRS) and lead loci (ARMS2, CFH) with AMD stages and features of high-risk nonlate AMD, including reticular pseudodrusen (RPD) and large drusen area (LDA).We performed a cross-sectional analysis of data from the Rhineland Study, a population-based study in Bonn, Germany. We included 4016 individuals aged 50 years and older of European descent. GRS and pathway-specific subscores were constructed based on a large genome-wide association study of AMD. Subscores were generated based on gene-pathways associations (complement, extracellular matrix remodeling (ECM) and lipid metabolism). Associations were assessed using logistic and multinomial regression.The mean age of participants was 63.36 years and 1813 (45.1%) were men. The GRS was positive in 48.1% of individuals and increased, but did not fully overlap, across AMD stages. Pathway-specific subscores increased across AMD stages except for the ECM subscore, which only showed a trend for increasing in late AMD. Increasing overall GRS was associated with RPD and LDA (OR [95%CI] for RPD: 1.70 [1.33-2.15], for LDA: 1.64 [1.29-2.07]) among individuals with AMD. Similarly, higher complement and ECM subscores was associated with RPD, while for LDA, only an association with complement subscore was observed.In a population-based setting, we confirmed higher genetic risk to be associated with more severe AMD and identified associations with high-risk features of intermediate AMD. Conjoint analyses suggested that high-risk features and late AMD might be differentially associated with genetic architecture in AMD, such as ECM remodeling. Incorporation of genetic information such as GRSs might improve AMD risk prediction strategies.
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000271698 650_7 $$2Other$$aAMD
000271698 650_7 $$2Other$$aPRS
000271698 650_7 $$2Other$$aRPD
000271698 650_7 $$2Other$$agenetics
000271698 650_7 $$2Other$$aretina
000271698 650_2 $$2MeSH$$aHumans
000271698 650_2 $$2MeSH$$aMale
000271698 650_2 $$2MeSH$$aFemale
000271698 650_2 $$2MeSH$$aCross-Sectional Studies
000271698 650_2 $$2MeSH$$aMiddle Aged
000271698 650_2 $$2MeSH$$aMacular Degeneration: genetics
000271698 650_2 $$2MeSH$$aMacular Degeneration: epidemiology
000271698 650_2 $$2MeSH$$aAged
000271698 650_2 $$2MeSH$$aGenetic Predisposition to Disease
000271698 650_2 $$2MeSH$$aGenome-Wide Association Study
000271698 650_2 $$2MeSH$$aRisk Factors
000271698 650_2 $$2MeSH$$aGermany: epidemiology
000271698 650_2 $$2MeSH$$aComplement Factor H: genetics
000271698 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide
000271698 650_2 $$2MeSH$$aRetinal Drusen: genetics
000271698 650_2 $$2MeSH$$aRetinal Drusen: epidemiology
000271698 650_2 $$2MeSH$$aProteins: genetics
000271698 650_2 $$2MeSH$$aPopulation Surveillance
000271698 650_2 $$2MeSH$$aDisease Progression
000271698 693__ $$0EXP:(DE-2719)Rhineland Study-20190321$$5EXP:(DE-2719)Rhineland Study-20190321$$eRhineland Study / Bonn$$x0
000271698 7001_ $$0P:(DE-2719)9002347$$aImtiaz, Mohammed Aslam$$b1
000271698 7001_ $$0P:(DE-2719)2811175$$aMauschitz, Matthias M$$b2
000271698 7001_ $$0P:(DE-2719)2812578$$aAziz, N. Ahmad$$b3
000271698 7001_ $$0P:(DE-HGF)0$$aHolz, Frank G$$b4
000271698 7001_ $$0P:(DE-2719)2810403$$aBreteler, Monique$$b5
000271698 7001_ $$0P:(DE-HGF)0$$aFinger, Robert P$$b6
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