{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:40:56Z","timestamp":1787586056728,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T00:00:00Z","timestamp":1710201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Medical University Hospital","award":["DMR-113-148"],"award-info":[{"award-number":["DMR-113-148"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. The prevalence and phenotypes of AMD differ among populations, including between people in Taiwan and other regions. We performed a genome-wide association study to identify genetic variants and to develop genetic models to predict the risk of AMD development and progression in the Taiwanese population. In total, 4039 patients with AMD and 16,488 non-AMD controls (aged \u2265 65 years) were included. We identified 31 AMD-associated variants (p &lt; 5 \u00d7 10\u22128) on chromosome 10q26, surrounding PLEKHA1-ARMS2-HTRA1. Two genetic models were constructed using the clump and threshold method. Model 1 included the single nucleotide polymorphism rs11200630 and showed a 1.31-fold increase in the risk of AMD per risk allele (95% confidence interval (CI) = 1.20\u20131.43, p &lt; 0.001). In model 2, 1412 single-nucleotide polymorphisms were selected to construct a polygenic risk score (PRS). Individuals with the top 5% PRS had a 1.40-fold higher AMD risk compared with that of individuals with a PRS in the bottom quartile (95% CI = 1.04\u20131.89, p = 0.025). Moreover, the PRS in the upper quartile was related to a decreased age at AMD diagnosis by 0.62 years (95% CI = \u22121.15, \u22120.09, p = 0.023). Both genetic models provide useful predictive power for populations at high risk of AMD, affording a basis for identifying patients requiring close follow-up and early intervention.<\/jats:p>","DOI":"10.3390\/ijms25063230","type":"journal-article","created":{"date-parts":[[2024,3,12]],"date-time":"2024-03-12T12:14:40Z","timestamp":1710245680000},"page":"3230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Genetic Variants for Risk Prediction and Early Diagnosis of Age-Related Macular Degeneration in the Taiwanese Population"],"prefix":"10.3390","volume":"25","author":[{"given":"Yu-Chuen","family":"Huang","sequence":"first","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-8844","authenticated-orcid":false,"given":"Wen-Ling","family":"Liao","sequence":"additional","affiliation":[{"name":"Center for Personalized Medicine, China Medical University Hospital, Taichung 404327, Taiwan"},{"name":"Graduate Institute of Integrated Medicine, China Medical University, Taichung 404328, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ju","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Department of Ophthalmology, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9246-8756","authenticated-orcid":false,"given":"Yu-Te","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Wen","family":"Chang","sequence":"additional","affiliation":[{"name":"Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2729-0541","authenticated-orcid":false,"given":"Ting-Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chia","family":"Chen","sequence":"additional","affiliation":[{"name":"Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel L.","family":"Weng","sequence":"additional","affiliation":[{"name":"American School in Taichung, Taichung 406051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuu-Jen","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404328, Taiwan"},{"name":"Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung 404327, Taiwan"},{"name":"Department of Medical Genetics, China Medical University Hospital, Taichung 404327, Taiwan"},{"name":"Children\u2019s Hospital of China Medical University, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e339","DOI":"10.1016\/S2214-109X(13)70113-X","article-title":"Causes of vision loss worldwide, 1990\u20132010: A systematic analysis","volume":"1","author":"Bourne","year":"2013","journal-title":"Lancet Glob. Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/S0140-6736(18)31550-2","article-title":"Age-related macular degeneration","volume":"392","author":"Mitchell","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(12)60282-7","article-title":"Age-related macular degeneration","volume":"379","author":"Lim","year":"2012","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/nrn2007","article-title":"Macular degeneration: Recent advances and therapeutic opportunities","volume":"7","author":"Rattner","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1111\/ceo.13580","article-title":"Prevalence of age-related macular degeneration in Chinese populations worldwide: A systematic review and meta-analysis","volume":"47","author":"Jin","year":"2019","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.ophtha.2009.10.007","article-title":"The prevalence of age-related macular degeneration in Asians: A systematic review and meta-analysis","volume":"117","author":"Kawasaki","year":"2010","journal-title":"Ophthalmology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/j.ophtha.2005.12.013","article-title":"Prevalence of age-related macular degeneration in 4 racial\/ethnic groups in the multi-ethnic study of atherosclerosis","volume":"113","author":"Klein","year":"2006","journal-title":"Ophthalmology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1038\/s41572-021-00265-2","article-title":"Age-related macular degeneration","volume":"7","author":"Fleckenstein","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1167\/iovs.08-1803","article-title":"Prevalence and associated risk factors of age-related macular degeneration in an elderly Chinese population in Taiwan: The Shihpai Eye Study","volume":"49","author":"Chen","year":"2008","journal-title":"Investig. Opthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1001\/archopht.121.6.785","article-title":"Progression of age-related macular degeneration: Association with body mass index, waist circumference, and waist-hip ratio","volume":"121","author":"Seddon","year":"2003","journal-title":"Arch. Ophthalmol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"895147","DOI":"10.1155\/2013\/895147","article-title":"Smoking and Age-Related Macular Degeneration: Review and Update","volume":"2013","author":"Velilla","year":"2013","journal-title":"J. Ophthalmol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1001\/jama.1996.03540140029022","article-title":"A prospective study of cigarette smoking and age-related macular degeneration in women","volume":"276","author":"Seddon","year":"1996","journal-title":"JAMA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1001\/archopht.123.3.321","article-title":"The US twin study of age-related macular degeneration: Relative roles of genetic and environmental influences","volume":"123","author":"Seddon","year":"2005","journal-title":"Arch. Ophthalmol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1076\/opep.10.5.315.17317","article-title":"Twin study of age-related macular degeneration","volume":"10","author":"Grizzard","year":"2003","journal-title":"Ophthalmic Epidemiol."},{"key":"ref_15","first-page":"775","article-title":"A twin study on age-related macular degeneration","volume":"92","author":"Meyers","year":"1994","journal-title":"Trans. Am. Ophthalmol. Soc."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","article-title":"A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants","volume":"48","author":"Fritsche","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2644","DOI":"10.1016\/j.ophtha.2013.07.053","article-title":"Prediction of age-related macular degeneration in the general population: The Three Continent AMD Consortium","volume":"120","author":"Buitendijk","year":"2013","journal-title":"Ophthalmology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ophtha.2023.08.023","article-title":"Genome-Wide Meta-analysis Identifies Risk Loci and Improves Disease Prediction of Age-Related Macular Degeneration","volume":"131","author":"He","year":"2024","journal-title":"Ophthalmology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6063","DOI":"10.1038\/ncomms7063","article-title":"New loci and coding variants confer risk for age-related macular degeneration in East Asians","volume":"6","author":"Cheng","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.preteyeres.2009.10.001","article-title":"Polypoidal choroidal vasculopathy and neovascular age-related macular degeneration: Same or different disease?","volume":"29","author":"Laude","year":"2010","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1064659","DOI":"10.3389\/fgene.2023.1064659","article-title":"Genome-wide association study and identification of systemic comorbidities in development of age-related macular degeneration in a hospital-based cohort of Han Chinese","volume":"14","author":"Shih","year":"2023","journal-title":"Front. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ophtha.2010.06.040","article-title":"Complement factor H Y402H variant and risk of age-related macular degeneration in Asians: A systematic review and meta-analysis","volume":"118","author":"Kondo","year":"2011","journal-title":"Ophthalmology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1097\/IAE.0b013e31814cef3a","article-title":"HTRA1 polymorphism in dry and wet age-related macular degeneration","volume":"28","author":"Lin","year":"2008","journal-title":"Retina"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e2103617118","DOI":"10.1073\/pnas.2103617118","article-title":"Chromosome 10q26\u2013driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium","volume":"118","author":"Williams","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7227","DOI":"10.1073\/pnas.0501536102","article-title":"A common haplotype in the complement regulatory gene factor H (HF1\/CFH) predisposes individuals to age-related macular degeneration","volume":"102","author":"Hageman","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1086\/444437","article-title":"Susceptibility genes for age-related maculopathy on chromosome 10q26","volume":"77","author":"Jakobsdottir","year":"2005","journal-title":"Am. J. Hum. Genet."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1097\/IAE.0b013e318184661d","article-title":"Complement factor H variant increases the risk for early age-related macular degeneration","volume":"28","author":"Lin","year":"2008","journal-title":"Retina"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Magnusson, K.P., Duan, S., Sigurdsson, H., Petursson, H., Yang, Z., Zhao, Y., Bernstein, P.S., Ge, J., Jonasson, F., and Stefansson, E. (2006). CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD. PLoS Med., 3.","DOI":"10.1371\/journal.pmed.0030005"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kim, J.E., Tomkins-Netzer, O., Elman, M.J., Lally, D.R., Goldstein, M., Goldenberg, D., Shulman, S., Benyamini, G., and Loewenstein, A. (2022). Evaluation of a self-imaging SD-OCT system designed for remote home monitoring. BMC Ophthalmol., 22.","DOI":"10.1186\/s12886-022-02458-z"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"57","DOI":"10.37796\/2211-8039.1302","article-title":"Comparison of multiple imputation algorithms and verification using whole-genome sequencing in the CMUH genetic biobank","volume":"11","author":"Liu","year":"2021","journal-title":"Biomedicine"},{"key":"ref_31","first-page":"5321","article-title":"Population structure of Han Chinese in the modern Taiwanese population based on 10,000 participants in the Taiwan Biobank project","volume":"25","author":"Chen","year":"2016","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"842673","DOI":"10.3389\/fendo.2022.842673","article-title":"Analysis of HLA Variants and Graves\u2019 Disease and Its Comorbidities Using a High Resolution Imputation System to Examine Electronic Medical Health Records","volume":"13","author":"Liao","year":"2022","journal-title":"Front. Endocrinol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nmeth.2307","article-title":"Improved whole-chromosome phasing for disease and population genetic studies","volume":"10","author":"Delaneau","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/ng.2354","article-title":"Fast and accurate genotype imputation in genome-wide association studies through pre-phasing","volume":"44","author":"Howie","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nature15394","article-title":"An integrated map of structural variation in 2504 human genomes","volume":"526","author":"Sudmant","year":"2015","journal-title":"Nature"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"giz082","DOI":"10.1093\/gigascience\/giz082","article-title":"PRSice-2: Polygenic Risk Score software for biobank-scale data","volume":"8","author":"Choi","year":"2019","journal-title":"GigaScience"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"s13742-015","DOI":"10.1186\/s13742-015-0047-8","article-title":"Second-generation PLINK: Rising to the challenge of larger and richer datasets","volume":"4","author":"Chang","year":"2015","journal-title":"GigaScience"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","article-title":"Haploview: Analysis and visualization of LD and haplotype maps","volume":"21","author":"Barrett","year":"2005","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3230\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:12:28Z","timestamp":1760105548000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/6\/3230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,12]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ijms25063230"],"URL":"https:\/\/doi.org\/10.3390\/ijms25063230","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,12]]}}}