{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:34:28Z","timestamp":1792805668979,"version":"4.5.0"},"reference-count":111,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,12,1]],"date-time":"2022-12-01T00:00:00Z","timestamp":1669852800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T00:00:00Z","timestamp":1662854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007747","name":"University of Utah","doi-asserted-by":"publisher","award":["R01 EY031209"],"award-info":[{"award-number":["R01 EY031209"]}],"id":[{"id":"10.13039\/100007747","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY022310"],"award-info":[{"award-number":["EY022310"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY024605"],"award-info":[{"award-number":["EY024605"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["EY030614"],"award-info":[{"award-number":["EY030614"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EY019007"],"award-info":[{"award-number":["P30EY019007"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY028203"],"award-info":[{"award-number":["R01EY028203"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY028954"],"award-info":[{"award-number":["R01EY028954"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY029315"],"award-info":[{"award-number":["R01EY029315"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001116","name":"Foundation Fighting Blindness","doi-asserted-by":"publisher","award":["PPA-1218-0751-COLU"],"award-info":[{"award-number":["PPA-1218-0751-COLU"]}],"id":[{"id":"10.13039\/100001116","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["R01 EY014800"],"award-info":[{"award-number":["R01 EY014800"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001818","name":"Research to Prevent Blindness","doi-asserted-by":"publisher","award":["R24 EY017404"],"award-info":[{"award-number":["R24 EY017404"]}],"id":[{"id":"10.13039\/100001818","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Experimental Eye Research"],"published-print":{"date-parts":[[2022,12]]},"DOI":"10.1016\/j.exer.2022.109248","type":"journal-article","created":{"date-parts":[[2022,9,13]],"date-time":"2022-09-13T01:52:59Z","timestamp":1663033979000},"page":"109248","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":34,"special_numbering":"C","title":["Systems genomics in age-related macular degeneration"],"prefix":"10.1016","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0634-5408","authenticated-orcid":false,"given":"Anneke I.","family":"den Hollander","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Mullins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz D.","family":"Orozco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew P.","family":"Voigt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsu-Hsin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Strunz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Grassmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan L.","family":"Haines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonas J.W.","family":"Kuiper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Santa J.","family":"Tumminia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rando","family":"Allikmets","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory S.","family":"Hageman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight","family":"Stambolian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C.W.","family":"Klaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jef D.","family":"Boeke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee","family":"Honigberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Katti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Frazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard H.F.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael B.","family":"Gorin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.exer.2022.109248_bib1","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s12551-018-0435-2","article-title":"Genomic approaches for the elucidation of genes and gene networks underlying cardiovascular traits","volume":"10","author":"Adriaens","year":"2018","journal-title":"Biophys. Rev."},{"key":"10.1016\/j.exer.2022.109248_bib2","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.ophtha.2020.08.031","article-title":"Predicting progression to advanced age-related macular degeneration from clinical, genetic, and lifestyle factors using machine learning","volume":"128","author":"Ajana","year":"2021","journal-title":"Ophthalmology"},{"key":"10.1016\/j.exer.2022.109248_bib3","series-title":"13th International Conference on Complement Therapeutics","article-title":"Recombinant complement factor H (GEM103) ocular biodisbribution and activity following intravitreal administration in cynomolgus monkeys","author":"Biggs","year":"2021"},{"key":"10.1016\/j.exer.2022.109248_bib4","first-page":"3699","article-title":"Age-related macular degeneration associated Complement Factor H variants show impaired functionality in vitro","volume":"61","author":"Biggs","year":"2020","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib5","series-title":"13th International Conference on Complement Therapeutics","article-title":"Mechanism of action of GEM103 (rhCFH) as a therapeutic in AMD","author":"Biggs","year":"2021"},{"key":"10.1016\/j.exer.2022.109248_bib6","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-50420-9","article-title":"CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex","volume":"9","author":"Borras","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2022.109248_bib7","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2023952118","article-title":"A versatile platform for locus-scale genome rewriting and verification","volume":"118","author":"Brosh","year":"2021","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib8","doi-asserted-by":"crossref","first-page":"6167","DOI":"10.1167\/iovs.14-15142","article-title":"Direct-to-consumer personal genome testing for age-related macular degeneration","volume":"55","author":"Buitendijk","year":"2014","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib9","doi-asserted-by":"crossref","first-page":"7401","DOI":"10.1073\/pnas.0912702107","article-title":"Genetic variants near TIMP3 and high-density lipoprotein-associated loci influence susceptibility to age-related macular degeneration","volume":"107","author":"Chen","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib10","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1080\/02713683.2020.1740744","article-title":"Unstimulated, serum-free cultures of retinal pigment epithelium excrete large mounds of drusen-like deposits","volume":"45","author":"Chen","year":"2020","journal-title":"Curr. Eye Res."},{"key":"10.1016\/j.exer.2022.109248_bib11","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/s41467-020-14499-3","article-title":"Increased circulating levels of Factor H-Related Protein 4 are strongly associated with age-related macular degeneration","volume":"11","author":"Cipriani","year":"2020","journal-title":"Nat. Commun."},{"key":"10.1016\/j.exer.2022.109248_bib12","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.ajhg.2021.05.015","article-title":"Beyond factor H: the impact of genetic-risk variants for age-related macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations","volume":"108","author":"Cipriani","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib13","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.1016\/j.neuron.2019.04.010","article-title":"Single-cell RNA-seq analysis of retinal development identifies NFI factors as regulating mitotic exit and late-born cell specification","volume":"102","author":"Clark","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.exer.2022.109248_bib14","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.ophtha.2020.11.024","article-title":"Genetic risk, lifestyle, and age-related macular degeneration in europe: the EYE-RISK consortium","volume":"128","author":"Colijn","year":"2021","journal-title":"Ophthalmology"},{"key":"10.1016\/j.exer.2022.109248_bib15","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.cell.2020.08.013","article-title":"Cell types of the human retina and its organoids at single-cell resolution","volume":"182","author":"Cowan","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.exer.2022.109248_bib16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-28471-8_1","article-title":"Pluripotent stem cells to model degenerative retinal diseases: the RPE perspective","volume":"1186","author":"Dalvi","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.exer.2022.109248_bib17","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/j.ophtha.2020.07.037","article-title":"Development of a genotype Assay for age-related macular degeneration: the EYE-RISK consortium","volume":"128","author":"de Breuk","year":"2021","journal-title":"Ophthalmology"},{"key":"10.1016\/j.exer.2022.109248_bib18","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1001\/jamaophthalmol.2021.4102","article-title":"Evaluating the occurrence of rare variants in the complement factor H gene in patients with early-onset drusen maculopathy","volume":"139","author":"de Breuk","year":"2021","journal-title":"JAMA Ophthalmol."},{"key":"10.1016\/j.exer.2022.109248_bib19","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/hmg\/ddab256","article-title":"Systemic complement levels in patients with age-related macular degeneration carrying rare or low frequency variants in the CFH gene","volume":"31","author":"de Jong","year":"2022","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib20","doi-asserted-by":"crossref","first-page":"100952","DOI":"10.1016\/j.preteyeres.2021.100952","article-title":"Implications of genetic variation in the complement system in age-related macular degeneration","volume":"84","author":"de Jong","year":"2021","journal-title":"Prog. Retin. Eye Res."},{"key":"10.1016\/j.exer.2022.109248_bib21","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1093\/hmg\/ddaa114","article-title":"Effect of rare coding variants in the CFI gene on Factor I expression levels","volume":"29","author":"de Jong","year":"2020","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib22","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.ajo.2018.09.036","article-title":"Intake of vegetables, fruit, and fish is beneficial for age-related macular degeneration","volume":"198","author":"de Koning-Backus","year":"2019","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.exer.2022.109248_bib23","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1126\/science.1110189","article-title":"Complement factor H polymorphism and age-related macular degeneration","volume":"308","author":"Edwards","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.exer.2022.109248_bib24","doi-asserted-by":"crossref","first-page":"9679","DOI":"10.1038\/s41598-018-28143-0","article-title":"C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway","volume":"8","author":"Fernandez-Godino","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2022.109248_bib25","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1001\/jamaophthalmol.2015.0814","article-title":"Phenotypic characterization of complement factor H R1210C rare genetic variant in age-related macular degeneration","volume":"133","author":"Ferrara","year":"2015","journal-title":"JAMA Ophthalmol."},{"key":"10.1016\/j.exer.2022.109248_bib26","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/ng.2578","article-title":"Seven new loci associated with age-related macular degeneration","volume":"45","author":"Fritsche","year":"2013","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib27","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":"10.1016\/j.exer.2022.109248_bib28","doi-asserted-by":"crossref","first-page":"E8214","DOI":"10.1073\/pnas.1710430114","article-title":"Drusen in patient-derived hiPSC-RPE models of macular dystrophies","volume":"114","author":"Galloway","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib29","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jclinepi.2015.09.016","article-title":"Million Veteran Program: a mega-biobank to study genetic influences on health and disease","volume":"70","author":"Gaziano","year":"2016","journal-title":"J. Clin. Epidemiol."},{"key":"10.1016\/j.exer.2022.109248_bib30","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.molimm.2016.11.016","article-title":"The complement system in age-related macular degeneration: a review of rare genetic variants and implications for personalized treatment","volume":"84","author":"Geerlings","year":"2017","journal-title":"Mol. Immunol."},{"key":"10.1016\/j.exer.2022.109248_bib31","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1004383","article-title":"Bayesian test for colocalisation between pairs of genetic association studies using summary statistics","volume":"10","author":"Giambartolomei","year":"2014","journal-title":"PLoS Genet."},{"key":"10.1016\/j.exer.2022.109248_bib32","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/ng1750","article-title":"Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration","volume":"38","author":"Gold","year":"2006","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib33","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1001\/jamaophthalmol.2019.1318","article-title":"Assessment of novel genome-wide significant gene loci and lesion growth in geographic atrophy secondary to age-related macular degeneration","volume":"137","author":"Grassmann","year":"2019","journal-title":"JAMA Ophthalmol."},{"key":"10.1016\/j.exer.2022.109248_bib34","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/s13073-017-0418-0","article-title":"Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits","volume":"9","author":"Grassmann","year":"2017","journal-title":"Genome Med."},{"key":"10.1016\/j.exer.2022.109248_bib35","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. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib36","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1126\/science.1110359","article-title":"Complement factor H variant increases the risk of age-related macular degeneration","volume":"308","author":"Haines","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.exer.2022.109248_bib37","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1167\/iovs.61.6.18","article-title":"Rare genetic variants in complement factor I lead to low FI plasma levels resulting in increased risk of age-related macular degeneration","volume":"61","author":"Hallam","year":"2020","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib38","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1093\/hmg\/ddp472","article-title":"Genetic control of the alternative pathway of complement in humans and age-related macular degeneration","volume":"19","author":"Hecker","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib39","doi-asserted-by":"crossref","first-page":"6611","DOI":"10.1038\/s41598-019-43144-3","article-title":"Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration","volume":"9","author":"Heesterbeek","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2022.109248_bib40","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1038\/ng.2740","article-title":"A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration","volume":"45","author":"Helgason","year":"2013","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib41","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1038\/ng1890","article-title":"A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration","volume":"38","author":"Hughes","year":"2006","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib42","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1167\/tvst.9.9.37","article-title":"Functional analysis of rare genetic variants in complement factor I (CFI) using a serum-based assay in advanced age-related macular degeneration","volume":"9","author":"Java","year":"2020","journal-title":"Transl. Vis. Sci. Technol."},{"key":"10.1016\/j.exer.2022.109248_bib43","doi-asserted-by":"crossref","first-page":"18277","DOI":"10.1073\/pnas.1109703108","article-title":"Cell culture model that mimics drusen formation and triggers complement activation associated with age-related macular degeneration","volume":"108","author":"Johnson","year":"2011","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib44","first-page":"3861","article-title":"Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels","volume":"24","author":"Kavanagh","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib45","doi-asserted-by":"crossref","first-page":"4870","DOI":"10.1167\/iovs.15-17009","article-title":"Assessment of proteins associated with complement activation and inflammation in maculae of human donors homozygous risk at chromosome 1 CFH-to-F13B","volume":"56","author":"Keenan","year":"2015","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib46","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.ajo.2021.06.017","article-title":"Phase 1 study of the anti-HtrA1 antibody-binding fragment FHTR2163 in geographic atrophy secondary to age-related macular degeneration","volume":"232","author":"Khanani","year":"2021","journal-title":"Am. J. Ophthalmol."},{"key":"10.1016\/j.exer.2022.109248_bib47","doi-asserted-by":"crossref","DOI":"10.3390\/cells9102257","article-title":"Pleiotropic locus 15q24.1 reveals a gender-specific association with neovascular but not atrophic age-related macular degeneration (AMD)","volume":"9","author":"Kiel","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.exer.2022.109248_bib48","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1126\/science.1109557","article-title":"Complement factor H polymorphism in age-related macular degeneration","volume":"308","author":"Klein","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.exer.2022.109248_bib49","doi-asserted-by":"crossref","first-page":"3703","DOI":"10.1073\/pnas.1814014116","article-title":"Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice","volume":"116","author":"Landowski","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib50","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/pcmedi\/pby019","article-title":"Big DNA as a tool to dissect an age-related macular degeneration-associated haplotype","volume":"2","author":"Laurent","year":"2019","journal-title":"Precis. Clin. Med."},{"key":"10.1016\/j.exer.2022.109248_bib51","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1042\/BIO04103046","article-title":"Probing the dark matter of the human genome with big DNA","volume":"4","author":"Laurent","year":"2019","journal-title":"Biochem"},{"key":"10.1016\/j.exer.2022.109248_bib52","doi-asserted-by":"crossref","first-page":"BIO88","DOI":"10.1167\/iovs.17-21809","article-title":"Omics biomarkers in Ophthalmology","volume":"58","author":"Lauwen","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib53","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":"10.1016\/j.exer.2022.109248_bib54","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/j.ajhg.2021.06.002","article-title":"Common haplotypes at the CFH locus and low-frequency variants in CFHR2 and CFHR5 associate with systemic FHR concentrations and age-related macular degeneration","volume":"108","author":"Lores-Motta","year":"2021","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib55","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2018100811","article-title":"A single-cell transcriptome atlas of the adult human retina","volume":"38","author":"Lukowski","year":"2019","journal-title":"EMBO J."},{"key":"10.1016\/j.exer.2022.109248_bib56","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2020.107939","article-title":"Choriocapillaris dropout in early age-related macular degeneration","volume":"192","author":"Lutty","year":"2020","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109248_bib57","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-021-95122-3","article-title":"Implication of specific retinal cell-type involvement and gene expression changes in AMD progression using integrative analysis of single-cell and bulk RNA-seq profiling","volume":"11","author":"Lyu","year":"2021","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2022.109248_bib58","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.cell.2015.05.002","article-title":"Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets","volume":"161","author":"Macosko","year":"2015","journal-title":"Cell"},{"key":"10.1016\/j.exer.2022.109248_bib59","article-title":"PO329-Phase 2a open label study of GEM103 in genetically selected geographic atrophy (GA) subjects","author":"Maturi","year":"2021","journal-title":"Am. Acad. Ophthalmol"},{"key":"10.1016\/j.exer.2022.109248_bib60","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.cell.2010.03.032","article-title":"Genetic heterogeneity in human disease","volume":"141","author":"McClellan","year":"2010","journal-title":"Cell"},{"key":"10.1016\/j.exer.2022.109248_bib61","doi-asserted-by":"crossref","first-page":"4902","DOI":"10.1038\/s41467-019-12780-8","article-title":"Single-cell transcriptomic atlas of the human retina identifies cell types associated with age-related macular degeneration","volume":"10","author":"Menon","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.exer.2022.109248_bib62","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1167\/iovs.10-6476","article-title":"Choriocapillaris vascular dropout related to density of drusen in human eyes with early age-related macular degeneration","volume":"52","author":"Mullins","year":"2011","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib63","doi-asserted-by":"crossref","first-page":"7395","DOI":"10.1073\/pnas.0912019107","article-title":"Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC)","volume":"107","author":"Neale","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib64","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1016\/j.celrep.2019.12.082","article-title":"Integration of eQTL and a single-cell atlas in the human eye identifies causal genes for age-related macular degeneration","volume":"30","author":"Orozco","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.exer.2022.109248_bib65","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.stemcr.2017.03.012","article-title":"iPSCORE: a resource of 222 iPSC lines enabling functional characterization of genetic variation across a variety of cell types","volume":"8","author":"Panopoulos","year":"2017","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.exer.2022.109248_bib66","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1186\/s40246-021-00359-8","article-title":"Protective chromosome 1q32 haplotypes mitigate risk for age-related macular degeneration associated with the CFH-CFHR5 and ARMS2\/HTRA1 loci","volume":"15","author":"Pappas","year":"2021","journal-title":"Hum. Genom."},{"key":"10.1016\/j.exer.2022.109248_bib67","doi-asserted-by":"crossref","first-page":"E3984","DOI":"10.1073\/pnas.1704117114","article-title":"Structural variants caused by Alu insertions are associated with risks for many human diseases","volume":"114","author":"Payer","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib68","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.cell.2019.01.004","article-title":"Molecular classification and comparative taxonomics of foveal and peripheral cells in primate retina","volume":"176","author":"Peng","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.exer.2022.109248_bib69","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.cell.2019.08.051","article-title":"Genome-wide association studies in ancestrally diverse populations: opportunities, methods, pitfalls, and recommendations","volume":"179","author":"Peterson","year":"2019","journal-title":"Cell"},{"key":"10.1016\/j.exer.2022.109248_bib70","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.ajhg.2014.03.004","article-title":"Joint analysis of functional genomic data and genome-wide association studies of 18 human traits","volume":"94","author":"Pickrell","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib71","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1167\/iovs.16-21060","article-title":"Subretinal pigment epithelial deposition of drusen components including hydroxyapatite in a primary cell culture model","volume":"58","author":"Pilgrim","year":"2017","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib72","doi-asserted-by":"crossref","first-page":"3300","DOI":"10.1038\/s41467-019-10936-0","article-title":"Mendelian randomization integrating GWAS and eQTL data reveals genetic determinants of complex and clinical traits","volume":"10","author":"Porcu","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.exer.2022.109248_bib73","doi-asserted-by":"crossref","first-page":"9113","DOI":"10.1074\/jbc.M114.548669","article-title":"Bisretinoid-mediated complement activation on retinal pigment epithelial cells is dependent on complement factor H haplotype","volume":"289","author":"Radu","year":"2014","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.exer.2022.109248_bib74","series-title":"The Structure of the Retina","author":"Ramon y Cajal","year":"1972"},{"key":"10.1016\/j.exer.2022.109248_bib75","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/s41588-019-0351-9","article-title":"Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration","volume":"51","author":"Ratnapriya","year":"2019","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib76","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1038\/ng.976","article-title":"A rare penetrant mutation in CFH confers high risk of age-related macular degeneration","volume":"43","author":"Raychaudhuri","year":"2011","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib77","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1038\/eye.2016.328","article-title":"Local complement activation in aqueous humor in patients with age-related macular degeneration","volume":"31","author":"Schick","year":"2017","journal-title":"Eye (Lond)"},{"key":"10.1016\/j.exer.2022.109248_bib78","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":"10.1016\/j.exer.2022.109248_bib79","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1167\/iovs.61.14.32","article-title":"Rare and common genetic variants, smoking, and body mass index: progression and earlier age of developing advanced age-related macular degeneration","volume":"61","author":"Seddon","year":"2020","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib80","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1038\/ng.2741","article-title":"Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration","volume":"45","author":"Seddon","year":"2013","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib81","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1016\/j.cell.2016.07.054","article-title":"Comprehensive classification of retinal bipolar neurons by single-cell transcriptomics","volume":"166","author":"Shekhar","year":"2016","journal-title":"Cell"},{"key":"10.1016\/j.exer.2022.109248_bib82","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.ophtha.2011.07.056","article-title":"Risk alleles in CFH and ARMS2 are independently associated with systemic complement activation in age-related macular degeneration","volume":"119","author":"Smailhodzic","year":"2012","journal-title":"Ophthalmology"},{"key":"10.1016\/j.exer.2022.109248_bib83","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.stemcr.2019.04.012","article-title":"Human iPSC-derived retinal pigment epithelium: a model system for prioritizing and functionally characterizing causal variants at AMD risk loci","volume":"12","author":"Smith","year":"2019","journal-title":"Stem Cell Rep."},{"key":"10.1016\/j.exer.2022.109248_bib84","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/j.celrep.2020.01.007","article-title":"Single-cell transcriptomic comparison of human fetal retina, hPSC-derived retinal organoids, and long-term retinal cultures","volume":"30","author":"Sridhar","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.exer.2022.109248_bib85","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1008934","article-title":"A mega-analysis of expression quantitative trait loci in retinal tissue","volume":"16","author":"Strunz","year":"2020","journal-title":"PLoS Genet."},{"key":"10.1016\/j.exer.2022.109248_bib86","doi-asserted-by":"crossref","DOI":"10.3390\/cells9102267","article-title":"Learning from fifteen years of genome-wide association studies in age-related macular degeneration","volume":"9","author":"Strunz","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.exer.2022.109248_bib87","doi-asserted-by":"crossref","first-page":"1584","DOI":"10.1038\/s41598-020-58510-9","article-title":"A transcriptome-wide association study based on 27 tissues identifies 106 genes potentially relevant for disease pathology in age-related macular degeneration","volume":"10","author":"Strunz","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2022.109248_bib88","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med."},{"key":"10.1016\/j.exer.2022.109248_bib89","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/s41586-018-0175-2","article-title":"Genomic atlas of the human plasma proteome","volume":"558","author":"Sun","year":"2018","journal-title":"Nature"},{"key":"10.1016\/j.exer.2022.109248_bib90","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/j.ophtha.2019.03.013","article-title":"Loss-of-Function mutations in the CFH gene affecting alternatively encoded factor H-like 1 protein cause dominant early-onset macular drusen","volume":"126","author":"Taylor","year":"2019","journal-title":"Ophthalmology"},{"key":"10.1016\/j.exer.2022.109248_bib91","first-page":"649","article-title":"Anti-angiogenic activity of Complement Factor H in laser-induced choroidal neovascularization mouse model","volume":"62","author":"Tellier","year":"2021","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib92","doi-asserted-by":"crossref","first-page":"2386","DOI":"10.1001\/jama.2009.812","article-title":"Mendelian randomization: nature's randomized trial in the post-genome era","volume":"301","author":"Thanassoulis","year":"2009","journal-title":"JAMA"},{"key":"10.1016\/j.exer.2022.109248_bib93","doi-asserted-by":"crossref","first-page":"9952","DOI":"10.1073\/pnas.1917608117","article-title":"Development of a therapeutic anti-HtrA1 antibody and the identification of DKK3 as a pharmacodynamic biomarker in geographic atrophy","volume":"117","author":"Tom","year":"2020","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib94","doi-asserted-by":"crossref","first-page":"E3040","DOI":"10.1073\/pnas.1424391112","article-title":"Regulation of age-related macular degeneration-like pathology by complement factor H","volume":"112","author":"Toomey","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib95","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1016\/j.neuron.2019.11.006","article-title":"Single-cell profiles of retinal ganglion cells differing in resilience to injury reveal neuroprotective genes","volume":"104","author":"Tran","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.exer.2022.109248_bib96","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1016\/j.survophthal.2020.10.008","article-title":"Revisiting the role of factor H in age-related macular degeneration: insights from complement-mediated renal disease and rare genetic variants","volume":"66","author":"Tzoumas","year":"2021","journal-title":"Surv. Ophthalmol."},{"key":"10.1016\/j.exer.2022.109248_bib97","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/ng.2640","article-title":"A functional variant in the CFI gene confers a high risk of age-related macular degeneration","volume":"45","author":"van de Ven","year":"2013","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib98","doi-asserted-by":"crossref","first-page":"24100","DOI":"10.1073\/pnas.1914143116","article-title":"Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration","volume":"116","author":"Voigt","year":"2019","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib99","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1093\/hmg\/ddab140","article-title":"Human photoreceptor cells from different macular subregions have distinct transcriptional profiles","volume":"30","author":"Voigt","year":"2021","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib100","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.exer.2019.05.001","article-title":"Molecular characterization of foveal versus peripheral human retina by single-cell RNA sequencing","volume":"184","author":"Voigt","year":"2019","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109248_bib101","doi-asserted-by":"crossref","DOI":"10.1016\/j.exer.2020.108204","article-title":"Spectacle: an interactive resource for ocular single-cell RNA sequencing data analysis","volume":"200","author":"Voigt","year":"2020","journal-title":"Exp. Eye Res."},{"key":"10.1016\/j.exer.2022.109248_bib102","doi-asserted-by":"crossref","DOI":"10.1038\/srep31531","article-title":"Mapping rare, deleterious mutations in Factor H: association with early onset, drusen burden, and lower antigenic levels in familial AMD","volume":"6","author":"Wagner","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2022.109248_bib103","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/nature10449","article-title":"Complement factor H binds malondialdehyde epitopes and protects from oxidative stress","volume":"478","author":"Weismann","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.exer.2022.109248_bib104","doi-asserted-by":"crossref","first-page":"6282","DOI":"10.1167\/iovs.12-9721","article-title":"Using flow cytometry to compare the dynamics of photoreceptor outer segment phagocytosis in iPS-derived RPE cells","volume":"53","author":"Westenskow","year":"2012","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"10.1016\/j.exer.2022.109248_bib105","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2103617118","article-title":"Chromosome 10q26-driven 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. U. S. A."},{"key":"10.1016\/j.exer.2022.109248_bib106","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1093\/hmg\/ddy002","article-title":"Genome-wide analysis of disease progression in age-related macular degeneration","volume":"27","author":"Yan","year":"2018","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib107","doi-asserted-by":"crossref","first-page":"9802","DOI":"10.1038\/s41598-020-66092-9","article-title":"Cell atlas of the human fovea and peripheral retina","volume":"10","author":"Yan","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.exer.2022.109248_bib108","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1056\/NEJMoa072618","article-title":"Complement C3 variant and the risk of age-related macular degeneration","volume":"357","author":"Yates","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.exer.2022.109248_bib109","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1093\/hmg\/ddr270","article-title":"Common variants near FRK\/COL10A1 and VEGFA are associated with advanced age-related macular degeneration","volume":"20","author":"Yu","year":"2011","journal-title":"Hum. Mol. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib110","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/ng.2758","article-title":"Identification of a rare coding variant in complement 3 associated with age-related macular degeneration","volume":"45","author":"Zhan","year":"2013","journal-title":"Nat. Genet."},{"key":"10.1016\/j.exer.2022.109248_bib111","doi-asserted-by":"crossref","first-page":"D983","DOI":"10.1093\/nar\/gkz888","article-title":"QTLbase: an integrative resource for quantitative trait loci across multiple human molecular phenotypes","volume":"48","author":"Zheng","year":"2020","journal-title":"Nucleic Acids Res."}],"container-title":["Experimental Eye Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522003281?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014483522003281?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T05:33:57Z","timestamp":1762148037000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014483522003281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12]]},"references-count":111,"alternative-id":["S0014483522003281"],"URL":"https:\/\/doi.org\/10.1016\/j.exer.2022.109248","relation":{},"ISSN":["0014-4835"],"issn-type":[{"value":"0014-4835","type":"print"}],"subject":[],"published":{"date-parts":[[2022,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Systems genomics in age-related macular degeneration","name":"articletitle","label":"Article Title"},{"value":"Experimental Eye Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.exer.2022.109248","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2022 The Author(s). Published by Elsevier Ltd.","name":"copyright","label":"Copyright"}],"article-number":"109248"}}