Common and rare genetic risk variants in age-related macular degeneration and genetic risk score in the Coimbra eye study.
| Title: | Common and rare genetic risk variants in age-related macular degeneration and genetic risk score in the Coimbra eye study. |
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| Authors: | Farinha C; AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Ophthalmology Department, Coimbra Hospital and Universitary Centre (CHUC), Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.; Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, (iCBR- FMUC), University of Coimbra, Coimbra, Portugal.; Barreto P; AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Coimbra R; AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Cachulo ML; AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Ophthalmology Department, Coimbra Hospital and Universitary Centre (CHUC), Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.; Melo JB; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal.; Cunha-Vaz J; AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, (iCBR- FMUC), University of Coimbra, Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal.; Lechanteur Y; Department of Ophthalmology, Radboud University Medical Center, Donders Institute for Brain Cognition and Behaviour, Nijmegan, Netherlands.; Hoyng CB; Department of Ophthalmology, Radboud University Medical Center, Donders Institute for Brain Cognition and Behaviour, Nijmegan, Netherlands.; Silva R; AIBILI - Association for Innovation and Biomedical Research on Light and Image, Coimbra, Portugal.; Ophthalmology Department, Coimbra Hospital and Universitary Centre (CHUC), Coimbra, Portugal.; Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal.; Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, (iCBR- FMUC), University of Coimbra, Coimbra, Portugal.; Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, Coimbra, Portugal. |
| Source: | Acta ophthalmologica [Acta Ophthalmol] 2023 Mar; Vol. 101 (2), pp. 185-199. Date of Electronic Publication: 2022 Aug 29. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101468102 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1755-3768 (Electronic) Linking ISSN: 1755375X NLM ISO Abbreviation: Acta Ophthalmol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford, UK : Wiley-Blackwell; Original Publication: Oxford, UK ; Malden, MA : Blackwell Munksgaard |
| MeSH Terms: | Proteins*/genetics ; Macular Degeneration*/diagnosis ; Macular Degeneration*/epidemiology ; Macular Degeneration*/genetics; Complement Factor H/genetics ; High-Temperature Requirement A Serine Peptidase 1/genetics ; Humans ; Genotype ; Polymorphism, Single Nucleotide ; Risk Factors |
| Abstract: | Purpose: To determine the contribution of common and rare genetic variants in age-related macular degeneration (AMD) in a Portuguese population from the Coimbra Eye Study (CES), and the genetic risk score (GRS).; Methods: Participants underwent ophthalmologic examination and imaging. A centralized reading centre performed AMD staging. Genetic sequencing was carried out with the EYE-RISK assay. Sixty-nine single nucleotide polymorphisms (SNPs) were genotyped and tested for association with AMD. Case-control and progression-to-AMD analyses were performed using logistic regression to assess allelic odds ratio (OR) at a 95% confidence interval (CI) for each variant. GRS was calculated for cases/controls and progressors/non-progressors. Cumulative impact of rare variants was compared between cases/controls using logistic regression.; Results: In case-control analysis (237 cases/640 controls) variants associated with risk of disease were: ARMS2 rs10490924, ARMS2_HTRA1 rs3750846, CFH rs35292876, SLC16A8 rs8135665, TGFBR1 rs1626340. Major risk variants ARMS2/HTRA1 rs3750846, CFH rs570618 and C3 rs2230199 had unexpected lower allele frequency (AF), and the highest risk-conferring variant was a rare variant, CFH rs35292876 (OR, 2.668; p-value = 0.021). In progression-to-AMD analysis (137 progressors/630 non-progressors), variants associated with risk of progression were ARMS2 rs10490924, ARMS2_HTRA1 rs3750846, CFH rs35292876. GRS of cases/controls was 1.124 ± 1.187 and 0.645 ± 1.124 (p-value |
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| Contributed Indexing: | Keywords: Coimbra eye study; age-related macular degeneration; common genetic variants; genetic risk score; rare genetic variants; single nucleotide polymorphism |
| Substance Nomenclature: | 0 (Proteins); 80295-65-4 (Complement Factor H); EC 3.4.21.- (HTRA1 protein, human); EC 3.4.21.- (High-Temperature Requirement A Serine Peptidase 1) |
| Entry Date(s): | Date Created: 20220829 Date Completed: 20230217 Latest Revision: 20231213 |
| Update Code: | 20260130 |
| DOI: | 10.1111/aos.15232 |
| PMID: | 36036675 |
| Database: | MEDLINE |
Journal Article