Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/113806
DC Field | Value | Language |
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dc.contributor.author | Farinha, Cláudia | - |
dc.contributor.author | Barreto, Patrícia | - |
dc.contributor.author | Coimbra, Rita | - |
dc.contributor.author | Cachulo, Maria da Luz | - |
dc.contributor.author | Melo, Joana Barbosa | - |
dc.contributor.author | Cunha-Vaz, José | - |
dc.contributor.author | Lechanteur, Yara | - |
dc.contributor.author | Hoyng, Carel B. | - |
dc.contributor.author | Silva, Rufino | - |
dc.date.accessioned | 2024-03-05T09:23:17Z | - |
dc.date.available | 2024-03-05T09:23:17Z | - |
dc.date.issued | 2023-03 | - |
dc.identifier.issn | 1755-375X | - |
dc.identifier.issn | 1755-3768 | - |
dc.identifier.uri | https://hdl.handle.net/10316/113806 | - |
dc.description.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 < 0.001), and of progressors/non-progressors was 1.190 ± 1.178 and 0.669 ± 1.141 (p-value < 0.001). Higher proportion of pathogenic rare CFH variants was observed in cases (OR, 9.661; p-value < 0.001). Conclusions: Both common and rare variants were associated with AMD, but a CFH rare variant conferred the highest risk of disease while three major risk variants had a lower-than- expected AF in our population originary from a geographic region with lower prevalence of AMD. GRS was still significantly higher in AMD patients. Damaging CFH rare variants were cumulatively more common in AMD cases. | pt |
dc.language.iso | eng | pt |
dc.publisher | John Wiley & Sons Ltd | pt |
dc.relation | Novartis | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | pt |
dc.subject | age-related macular degeneration | pt |
dc.subject | Coimbra eye study | pt |
dc.subject | common genetic variants | pt |
dc.subject | genetic risk score | pt |
dc.subject | rare genetic variants | pt |
dc.subject | single nucleotide polymorphism | pt |
dc.title | Common and rare genetic risk variants in age-related macular degeneration and genetic risk score in the Coimbra eye study | pt |
dc.type | article | pt |
degois.publication.firstPage | 185 | pt |
degois.publication.lastPage | 199 | pt |
degois.publication.issue | 2 | pt |
degois.publication.title | Acta Ophthalmologica | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1111/aos.15232 | - |
degois.publication.volume | 101 | pt |
dc.date.embargo | 2023-03-01 | * |
dc.identifier.pmid | 36036675 | - |
uc.date.periodoEmbargo | 0 | pt |
dc.identifier.eissn | 1755-3768 | - |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0003-4596-0913 | - |
crisitem.author.orcid | 0000-0002-0900-4548 | - |
crisitem.author.orcid | 0000-0002-0947-9850 | - |
crisitem.author.orcid | 0000-0001-8676-0833 | - |
Appears in Collections: | I&D IBILI - Artigos em Revistas Internacionais I&D CIBB - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais I&D ICBR - Artigos em Revistas Internacionais |
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Acta Ophthalmologica - 2022 - Farinha - Common and rare genetic risk variants in age‐related macular degeneration and.pdf | 984.65 kB | Adobe PDF | View/Open |
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