{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:52:41Z","timestamp":1790617961110,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T00:00:00Z","timestamp":1661731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Ophthalmologica"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To determine the contribution of common and rare genetic variants in age\u2010related macular degeneration (AMD) in a Portuguese population from the Coimbra Eye Study (CES), and the genetic risk score (GRS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Participants underwent ophthalmologic examination and imaging. A centralized reading centre performed AMD staging. Genetic sequencing was carried out with the EYE\u2010RISK assay. Sixty\u2010nine single nucleotide polymorphisms (SNPs) were genotyped and tested for association with AMD. Case\u2013control and progression\u2010to\u2010AMD 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\u2010progressors. Cumulative impact of rare variants was compared between cases\/controls using logistic regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In case\u2013control analysis (237 cases\/640 controls) variants associated with risk of disease were: <jats:italic>ARMS2<\/jats:italic> rs10490924, <jats:italic>ARMS2_HTRA1<\/jats:italic> rs3750846, <jats:italic>CFH<\/jats:italic> rs35292876, <jats:italic>SLC16A8<\/jats:italic> rs8135665, <jats:italic>TGFBR1<\/jats:italic> rs1626340. Major risk variants <jats:italic>ARMS2\/HTRA1<\/jats:italic> rs3750846, <jats:italic>CFH<\/jats:italic> rs570618 and <jats:italic>C3<\/jats:italic> rs2230199 had unexpected lower allele frequency (AF), and the highest risk\u2010conferring variant was a rare variant, <jats:italic>CFH<\/jats:italic> rs35292876 (OR, 2.668; <jats:italic>p<\/jats:italic>\u2010value\u00a0=\u00a00.021). In progression\u2010to\u2010AMD analysis (137 progressors\/630 non\u2010progressors), variants associated with risk of progression were <jats:italic>ARMS2<\/jats:italic> rs10490924<jats:italic>, ARMS2_HTRA1<\/jats:italic> rs3750846<jats:italic>, CFH<\/jats:italic> rs35292876. GRS of cases\/controls was 1.124\u2009\u00b1\u20091.187 and 0.645\u2009\u00b1\u20091.124 (<jats:italic>p<\/jats:italic>\u2010value\u2009&lt;\u20090.001), and of progressors\/non\u2010progressors was 1.190\u2009\u00b1\u20091.178 and 0.669\u2009\u00b1\u20091.141 (<jats:italic>p<\/jats:italic>\u2010value\u2009&lt;\u20090.001). Higher proportion of pathogenic rare <jats:italic>CFH<\/jats:italic> variants was observed in cases (OR, 9.661; <jats:italic>p<\/jats:italic>\u2010value\u2009&lt;\u20090.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Both common and rare variants were associated with AMD, but a <jats:italic>CFH<\/jats:italic> rare variant conferred the highest risk of disease while three major risk variants had a lower\u2010than\u2010expected AF in our population originary from a geographic region with lower prevalence of AMD. GRS was still significantly higher in AMD patients. Damaging <jats:italic>CFH<\/jats:italic> rare variants were cumulatively more common in AMD cases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aos.15232","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T13:29:11Z","timestamp":1661779751000},"page":"185-199","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Common and rare genetic risk variants in age\u2010related macular degeneration and genetic risk score in the Coimbra eye study"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4596-0913","authenticated-orcid":false,"given":"Cl\u00e1udia","family":"Farinha","sequence":"first","affiliation":[{"name":"AIBILI \u2013 Association for Innovation and Biomedical Research on Light and Image  Coimbra Portugal"},{"name":"Ophthalmology Department Coimbra Hospital and Universitary Centre (CHUC)  Coimbra Portugal"},{"name":"Clinical Academic Center of Coimbra 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