{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T10:57:04Z","timestamp":1794567424053,"version":"4.9.1"},"reference-count":61,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:00Z","timestamp":1598400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HHSN268201200008I"],"award-info":[{"award-number":["HHSN268201200008I"]}],"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":["R01 EY RES 511967"],"award-info":[{"award-number":["R01 EY RES 511967"]}],"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":["R01 EY022310"],"award-info":[{"award-number":["R01 EY022310"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HE 3690\/5-1"],"award-info":[{"award-number":["HE 3690\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HE-3690\/5-1"],"award-info":[{"award-number":["HE-3690\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GR 5065\/1-1"],"award-info":[{"award-number":["GR 5065\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GR 5065\/1-1"],"award-info":[{"award-number":["GR 5065\/1-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01ER1206"],"award-info":[{"award-number":["01ER1206"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["01ER1507"],"award-info":[{"award-number":["01ER1507"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","award":["031L0026"],"award-info":[{"award-number":["031L0026"]}],"id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014913","name":"Free State of Saxony","doi-asserted-by":"crossref","award":["713-241202"],"award-info":[{"award-number":["713-241202"]}],"id":[{"id":"10.13039\/501100014913","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100014913","name":"Free State of Saxony","doi-asserted-by":"crossref","award":["14505\/2470"],"award-info":[{"award-number":["14505\/2470"]}],"id":[{"id":"10.13039\/501100014913","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100014913","name":"Free State of Saxony","doi-asserted-by":"crossref","award":["14575\/2470"],"award-info":[{"award-number":["14575\/2470"]}],"id":[{"id":"10.13039\/501100014913","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R21EY030142"],"award-info":[{"award-number":["R21EY030142"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R21EY030631"],"award-info":[{"award-number":["R21EY030631"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["R01EY030575"],"award-info":[{"award-number":["R01EY030575"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","award":["P30EYE003790"],"award-info":[{"award-number":["P30EYE003790"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Rhineland-Palatinate","award":["AZ 961-386261\/733"],"award-info":[{"award-number":["AZ 961-386261\/733"]}]},{"DOI":"10.13039\/501100013368","name":"Deutsche Akademie der Naturforscher Leopoldina - Nationale Akademie der Wissenschaften","doi-asserted-by":"publisher","award":["LPDS 2018-06"],"award-info":[{"award-number":["LPDS 2018-06"]}],"id":[{"id":"10.13039\/501100013368","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Helmut-Ecker-Foundation","award":["05\/17"],"award-info":[{"award-number":["05\/17"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Genomics"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and via an automated machine learning approach for &gt;\u2009170,000 photographs from UKBB. We searched for early AMD loci via GWAS and via a candidate approach based on 14 previously suggested early AMD variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Altogether, we identified 10 independent loci with statistical significance for early AMD: (i) 8 from our GWAS with genome-wide significance (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u20095\u2009\u00d7\u200910\n                      <jats:sup>\u2212\u20098<\/jats:sup>\n                      ), (ii) one previously suggested locus with experiment-wise significance (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u20090.05\/14) in our non-overlapping data and with genome-wide significance when combining the reported and our non-overlapping data (together 17,539 cases, 105,395 controls), and (iii) one further previously suggested locus with experiment-wise significance in our non-overlapping data. Of these 10 identified loci, 8 were novel and 2 known for early AMD. Most of the 10 loci overlapped with known advanced AMD loci (near\n                      <jats:italic>ARMS2\/HTRA1, CFH<\/jats:italic>\n                      ,\n                      <jats:italic>C2<\/jats:italic>\n                      ,\n                      <jats:italic>C3<\/jats:italic>\n                      ,\n                      <jats:italic>CETP<\/jats:italic>\n                      ,\n                      <jats:italic>TNFRSF10A<\/jats:italic>\n                      ,\n                      <jats:italic>VEGFA, APOE<\/jats:italic>\n                      ), except two that have not yet been identified with statistical significance for any AMD. Among the 17 genes within these two loci, in-silico functional annotation suggested\n                      <jats:italic>CD46<\/jats:italic>\n                      and\n                      <jats:italic>TYR<\/jats:italic>\n                      as the most likely responsible genes. Presence or absence of an early AMD effect distinguished the known pathways of advanced AMD genetics (complement\/lipid pathways versus extracellular matrix metabolism).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our GWAS on early AMD identified novel loci, highlighted shared and distinct genetics between early and advanced AMD and provides insights into AMD etiology. Our data provide a resource comparable in size to the existing IAMDGC data on advanced AMD genetics enabling a joint view. The biological relevance of this joint view is underscored by the ability of early AMD effects to differentiate the major pathways for advanced AMD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12920-020-00760-7","type":"journal-article","created":{"date-parts":[[2020,8,26]],"date-time":"2020-08-26T00:00:32Z","timestamp":1598400032000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":141,"title":["Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease"],"prefix":"10.1186","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0292-5421","authenticated-orcid":false,"given":"Thomas W.","family":"Winkler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Grassmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Brandl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Kiel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"G\u00fcnther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Strunz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Weidner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina E.","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina A.","family":"Korb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alicia","family":"Poplawski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander K.","family":"Schuster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"M\u00fcller-Nurasyid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Peters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska G.","family":"Rauscher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Elze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrin","family":"Horn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Scholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Ca\u00f1adas-Garre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy Jayne","family":"McKnight","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth E.","family":"Hogg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helmut","family":"K\u00fcchenhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris M.","family":"Heid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus J.","family":"Stark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard H. F.","family":"Weber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,8,26]]},"reference":[{"key":"760_CR1","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1016\/S0140-6736(12)60282-7","volume":"379","author":"LS Lim","year":"2012","unstructured":"Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. Lancet Elsevier. 2012;379:1728\u201338.","journal-title":"Lancet Elsevier"},{"key":"760_CR2","doi-asserted-by":"crossref","first-page":"AMD48","DOI":"10.1167\/iovs.18-24158","volume":"59","author":"ST Garrity","year":"2018","unstructured":"Garrity ST, Sarraf D, Freund KB, Sadda SR. Multimodal imaging of Nonneovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2018;59:AMD48\u201364.","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"760_CR3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/j.1755-3768.2011.02331.x","volume":"90","author":"R Forte","year":"2012","unstructured":"Forte R, Querques G, Querques L, Massamba N, Le Tien V, Souied EH. Multimodal imaging of dry age-related macular degeneration. Acta Ophthalmol. 2012;90:281\u20137.","journal-title":"Acta Ophthalmol"},{"key":"760_CR4","doi-asserted-by":"crossref","first-page":"14","DOI":"10.3109\/09286586.2013.867512","volume":"21","author":"R Klein","year":"2014","unstructured":"Klein R, Meuer SM, Myers CE, Buitendijk GHS, Rochtchina E, Choudhury F, et al. Harmonizing the classification of age-related macular degeneration in the three-continent AMD consortium. Ophthalmic Epidemiol. 2014;21:14\u201323.","journal-title":"Ophthalmic Epidemiol"},{"key":"760_CR5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-26629-5","volume":"8","author":"C Brandl","year":"2018","unstructured":"Brandl C, Zimmermann ME, G\u00fcnther F, Barth T, Olden M, Schelter SC, et al. On the impact of different approaches to classify age-related macular degeneration: results from the German AugUR study. Sci Rep. 2018;8:1\u201310.","journal-title":"Sci Rep"},{"key":"760_CR6","doi-asserted-by":"crossref","first-page":"2224","DOI":"10.1016\/S0161-6420(00)00409-7","volume":"107","author":"AREDS","year":"2000","unstructured":"AREDS. Risk factors associated with age-related macular degeneration. A case-control study in the age-related eye disease study: age-related eye disease study report number 3. Age-Related Eye Disease Study Research Group. Ophthalmology. 2000;107:2224\u201332.","journal-title":"Ophthalmology"},{"key":"760_CR7","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1016\/S0161-6420(00)00580-7","volume":"108","author":"W Smith","year":"2001","unstructured":"Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, et al. Risk factors for age-related macular degeneration: pooled findings from three continents. Ophthalmology Elsevier. 2001;108:697\u2013704.","journal-title":"Ophthalmology Elsevier"},{"key":"760_CR8","doi-asserted-by":"crossref","first-page":"343","DOI":"10.3390\/jcm4020343","volume":"4","author":"Y Yonekawa","year":"2015","unstructured":"Yonekawa Y, Miller J, Kim I. Age-related macular degeneration: advances in management and diagnosis. J Clin Med. 2015;4:343\u201359.","journal-title":"J Clin Med"},{"key":"760_CR9","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ng.3448","volume":"48","author":"LG Fritsche","year":"2016","unstructured":"Fritsche LG, Igl W, Bailey JNC, Grassmann F, Sengupta S, Bragg-Gresham JL, et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat Genet. 2016;48:134\u201343.","journal-title":"Nat Genet"},{"key":"760_CR10","doi-asserted-by":"crossref","unstructured":"Grassmann F, Fritsche LG, Keilhauer CN, Heid IM, Weber BHF. Modelling the genetic risk in age-related macular degeneration. PLoS One. 2012;7.","DOI":"10.1371\/journal.pone.0037979"},{"key":"760_CR11","first-page":"1","volume":"10","author":"X Han","year":"2020","unstructured":"Han X, Gharahkhani P, Mitchell P, Liew G, Hewitt AW, MacGregor S. Genome-wide meta-analysis identifies novel loci associated with age-related macular degeneration. J. Hum. Genet. 2020;10:1.","journal-title":"J. Hum. Genet"},{"key":"760_CR12","doi-asserted-by":"crossref","first-page":"e53830","DOI":"10.1371\/journal.pone.0053830","volume":"8","author":"EG Holliday","year":"2013","unstructured":"Holliday EG, Smith AV, Cornes BK, Buitendijk GHS, Jensen RA, Sim X, et al. Insights into the Genetic Architecture of Early Stage Age-Related Macular Degeneration: A Genome-Wide Association Study Meta-Analysis. PLoS One. 2013;8:e53830.","journal-title":"PLoS One"},{"key":"760_CR13","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton A, Abecasis GR, Altshuler DM, Durbin RM, Bentley DR, Chakravarti A, et al. A global reference for human genetic variation. Nature. 2015;526:68\u201374.","journal-title":"Nature."},{"key":"760_CR14","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/ng.3643","volume":"48","author":"S McCarthy","year":"2016","unstructured":"McCarthy S, Das S, Kretzschmar W, Delaneau O, Wood AR, Teumer A, et al. A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet. 2016;48:1279\u201383.","journal-title":"Nat Genet"},{"key":"760_CR15","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1038\/nature14962","volume":"526","author":"K Walter","year":"2015","unstructured":"Walter K, Min JL, Huang J, Crooks L, Memari Y, McCarthy S, et al. The UK10K project identifies rare variants in health and disease. Nature. 2015;526:82\u20139.","journal-title":"Nature."},{"key":"760_CR16","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, et al. The UK biobank resource with deep phenotyping and genomic data. Nature. 2018;562:203\u20139.","journal-title":"Nature."},{"key":"760_CR17","first-page":"1403","volume":"252","author":"CA Korb","year":"2014","unstructured":"Korb CA, Kottler UB, Wolfram C, Hoehn R, Schulz A, Zwiener I, et al. Prevalence of age-related macular degeneration in a large European cohort: results from the population-based Gutenberg health study. Graefe\u2019s arch. Clin. Exp. Ophthalmol. Springer. Berlin Heidelberg. 2014;252:1403\u201311.","journal-title":"Berlin Heidelberg"},{"key":"760_CR18","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.ophtha.2012.10.036","volume":"120","author":"FL Ferris","year":"2013","unstructured":"Ferris FL, Wilkinson CP, Bird A, Chakravarthy U, Chew E, Csaky K, et al. Clinical classification of age-related macular degeneration. Ophthalmology. 2013;120:844\u201351.","journal-title":"Ophthalmology."},{"key":"760_CR19","doi-asserted-by":"crossref","first-page":"e0167181","DOI":"10.1371\/journal.pone.0167181","volume":"11","author":"C Brandl","year":"2016","unstructured":"Brandl C, Breinlich V, Stark KJ, Enzinger S, A\u00dfenmacher M, Olden M, et al. Features of Age-Related Macular Degeneration in the General Adults and Their Dependency on Age, Sex, and Smoking: Results from the German KORA Study. Thatcher TH, editor. PLoS One. Public Libr Sci. 2016;11:e0167181.","journal-title":"PLoS One. Public Libr Sci"},{"key":"760_CR20","doi-asserted-by":"crossref","first-page":"1410","DOI":"10.1016\/j.ophtha.2018.02.037","volume":"125","author":"F Grassmann","year":"2018","unstructured":"Grassmann F, Mengelkamp J, Brandl C, Harsch S, Zimmermann ME, Linkohr B, et al. A deep learning algorithm for prediction of age-related eye disease study severity scale for age-related macular degeneration from color fundus photography. Ophthalmology. 2018;125:1410\u201320.","journal-title":"Ophthalmology"},{"key":"760_CR21","doi-asserted-by":"crossref","unstructured":"Guenther F, Brandl C, Winkler TW, et al. Chances and challenges of machine learning-based disease classification in genetic association studies illustrated on age-related macular degeneration.\u00a0Genet Epidemiol. 2020;10.1002\/gepi.22336.","DOI":"10.1101\/867697"},{"key":"760_CR22","doi-asserted-by":"crossref","unstructured":"De Raadt A, Warrens MJ, Bosker RJ, HAL K. Kappa Coefficients for Missing Data. Educ. Psychol. Meas. 2019.","DOI":"10.1177\/0013164418823249"},{"key":"760_CR23","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1093\/bioinformatics\/btw079","volume":"32","author":"X Zhan","year":"2016","unstructured":"Zhan X, Hu Y, Li B, Abecasis GR, Liu DJ. RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data. Bioinformatics. 2016;32:1423\u20136.","journal-title":"Bioinformatics."},{"key":"760_CR24","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/gepi.22204","volume":"43","author":"M Gorski","year":"2019","unstructured":"Gorski M, G\u00fcnther F, Winkler TW, Weber BHF, Heid IM. On the differences between mega- and meta-imputation and analysis exemplified on the genetics of age-related macular degeneration. Genet Epidemiol. 2019;43:559\u201376.","journal-title":"Genet Epidemiol"},{"key":"760_CR25","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1038\/nprot.2014.071","volume":"9","author":"TW Winkler","year":"2014","unstructured":"Winkler TW, Day FR, Croteau-Chonka DC, Wood AR, Locke AE, M\u00e4gi R, et al. Quality control and conduct of genome-wide association meta-analyses. Nat Protoc. 2014;9:1192\u2013212.","journal-title":"Nat Protoc"},{"key":"760_CR26","first-page":"997","volume":"55","author":"AB Devlin","year":"2013","unstructured":"Devlin AB, Roeder K, Devlin B. Genomic Control for Association. 2013;55:997\u20131004.","journal-title":"Genomic Control for Association"},{"key":"760_CR27","doi-asserted-by":"crossref","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","volume":"26","author":"CJ Willer","year":"2010","unstructured":"Willer CJ, Li Y, Abecasis GR. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics. 2010;26:2190\u20131.","journal-title":"Bioinformatics."},{"key":"760_CR28","volume-title":"Doing meta-analysis in R: a hands-on guide","author":"M Harrer","year":"2019","unstructured":"Harrer M, Cuijpers P, Furukawa T, Ebert DD. Doing meta-analysis in R: a hands-on guide. Lab: Prot; 2019."},{"key":"760_CR29","doi-asserted-by":"crossref","unstructured":"Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA (editors). Cochrane Handbook for Systematic Reviews of Interventions. 2nd Edition. Chichester: Wiley; 2019.","DOI":"10.1002\/9781119536604"},{"key":"760_CR30","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1037\/1082-989X.11.2.193","volume":"11","author":"TB Huedo-Medina","year":"2006","unstructured":"Huedo-Medina TB, S\u00e1nchez-Meca J, Mar\u00edn-Mart\u00ednez F, Botella J. Assessing heterogeneity in meta-analysis: Q statistic or I 2 index? Psychol Methods. 2006;11:193\u2013206.","journal-title":"Psychol Methods"},{"key":"760_CR31","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/ng.2213","volume":"44","author":"J Yang","year":"2012","unstructured":"Yang J, Ferreira T, Morris AP, Medland SE, Madden PAF, Heath AC, et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat Genet Nature Publishing Group. 2012;44:369\u201375.","journal-title":"Nat Genet Nature Publishing Group"},{"key":"760_CR32","doi-asserted-by":"crossref","unstructured":"Kichaev G, Yang WY, Lindstrom S, Hormozdiari F, Eskin E, Price AL, et al. Integrating functional data to prioritize causal variants in statistical fine-mapping studies. PLoS Genet. 2014;10.","DOI":"10.1371\/journal.pgen.1004722"},{"key":"760_CR33","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13059-016-0974-4","volume":"17","author":"W McLaren","year":"2016","unstructured":"McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GRS, Thormann A, et al. The Ensembl Variant Effect Predictor. Genome Biol. 2016;17:122.","journal-title":"Genome Biol"},{"key":"760_CR34","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/s41588-019-0351-9","volume":"51","author":"R Ratnapriya","year":"2019","unstructured":"Ratnapriya R, Sosina OA, Starostik MR, Kwicklis M, Kapphahn RJ, Fritsche LG, et al. Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration. Nat Genet. 2019;51:606\u201310.","journal-title":"Nat Genet"},{"key":"760_CR35","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1038\/nature24277","volume":"550","author":"F Aguet","year":"2017","unstructured":"Aguet F, Brown AA, Castel SE, Davis JR, He Y, Jo B, et al. Genetic effects on gene expression across human tissues. Nature. 2017;550:204\u201313.","journal-title":"Nature."},{"key":"760_CR36","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1016\/j.ajhg.2016.10.003","volume":"99","author":"F Hormozdiari","year":"2016","unstructured":"Hormozdiari F, van de Bunt M, Segr\u00e8 AV, Li X, Joo JWJ, Bilow M, et al. Colocalization of GWAS and eQTL signals detects target genes. Am. J Hum Genet. 2016;99:1245\u201360.","journal-title":"J Hum Genet"},{"key":"760_CR37","doi-asserted-by":"crossref","first-page":"3325","DOI":"10.1093\/hmg\/ddy239","volume":"27","author":"JM Bryan","year":"2018","unstructured":"Bryan JM, Fufa TD, Bharti K, Brooks BP, Hufnagel RB, McGaughey DM. Identifying core biological processes distinguishing human eye tissues with precise systems-level gene expression analyses and weighted correlation networks. Hum Mol Genet Narnia. 2018;27:3325\u201339.","journal-title":"Hum Mol Genet Narnia"},{"key":"760_CR38","doi-asserted-by":"crossref","first-page":"D801","DOI":"10.1093\/nar\/gky1056","volume":"47","author":"CJ Bult","year":"2019","unstructured":"Bult CJ, Blake JA, Smith CL, Kadin JA, Richardson JE, Anagnostopoulos A, et al. Mouse genome database (MGD) 2019. Nucleic Acids Res Oxford University Press. 2019;47:D801\u20136.","journal-title":"Nucleic Acids Res Oxford University Press"},{"key":"760_CR39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13073-016-0392-y","volume":"9","author":"F Grassmann","year":"2017","unstructured":"Grassmann F, Kiel C, Zimmermann ME, Gorski M, Grassmann V, Stark K, et al. Genetic pleiotropy between age-related macular degeneration and 16 complex diseases and traits. Genome Med Genome Medicine. 2017;9:1\u201313.","journal-title":"Genome Med Genome Medicine"},{"key":"760_CR40","doi-asserted-by":"crossref","first-page":"D896","DOI":"10.1093\/nar\/gkw1133","volume":"45","author":"J MacArthur","year":"2017","unstructured":"MacArthur J, Bowler E, Cerezo M, Gil L, Hall P, Hastings E, et al. The new NHGRI-EBI catalog of published genome-wide association studies (GWAS catalog). Nucleic Acids Res. 2017;45:D896\u2013901.","journal-title":"Nucleic Acids Res"},{"key":"760_CR41","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/ejhg.2013.274","volume":"22","author":"T Beck","year":"2014","unstructured":"Beck T, Hastings RK, Gollapudi S, Free RC, Brookes AJ. GWAS central: a comprehensive resource for the comparison and interrogation of genome-wide association studies. Eur J Hum Genet Nature Publishing Group. 2014;22:949\u201352.","journal-title":"Eur J Hum Genet Nature Publishing Group"},{"key":"760_CR42","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1038\/s41588-018-0248-z","volume":"50","author":"O Canela-Xandri","year":"2018","unstructured":"Canela-Xandri O, Rawlik K, Tenesa A. An atlas of genetic associations in UK biobank. Nat Genet Springer US. 2018;50:1593\u20139.","journal-title":"Nat Genet Springer US"},{"key":"760_CR43","unstructured":"oav B, Hochberg Y. Controlling the False Discovery Rate - a Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B-Methodological 1995.pdf. JR Stat Soc Ser B. 1995."},{"key":"760_CR44","first-page":"1","volume":"13","author":"TW Winkler","year":"2018","unstructured":"Winkler TW, Brandl C, Grassmann F, Gorski M, Stark K, Loss J, et al. Investigating the modulation of genetic effects on late AMD by age and sex: lessons learned and two additional loci. PLoS One. 2018;13:1\u201321.","journal-title":"PLoS One"},{"key":"760_CR45","first-page":"291","volume":"47","author":"B Bulik-Sullivan","year":"2015","unstructured":"Bulik-Sullivan B, Loh PR, Finucane HK, Ripke S, Yang J, Patterson N, et al. LD score regression distinguishes confounding from polygenicity in genome-wide association studies. NatGenet Nature Publishing Group. 2015;47:291\u20135.","journal-title":"NatGenet Nature Publishing Group"},{"key":"760_CR46","doi-asserted-by":"crossref","unstructured":"Winkler TW, G\u00fcnther F, H\u00f6llerer S, Zimmermann M, Loos RJ, Kutalik Z, et al. A joint view on genetic variants for adiposity differentiates subtypes with distinct metabolic implications. Nat Commun Springer US. 2018;9.","DOI":"10.1038\/s41467-018-05088-6"},{"key":"760_CR47","doi-asserted-by":"crossref","first-page":"W90","DOI":"10.1093\/nar\/gkw377","volume":"44","author":"MV Kuleshov","year":"2016","unstructured":"Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z, et al. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res. 2016;44:W90\u20137.","journal-title":"Nucleic Acids Res"},{"key":"760_CR48","doi-asserted-by":"crossref","unstructured":"Gao X, Starmer J, Martin ER. A multiple testing correction method for genetic association studies using correlated single nucleotide polymorphisms. Genet Epidemiol. 2008.","DOI":"10.1002\/gepi.20310"},{"key":"760_CR49","doi-asserted-by":"crossref","first-page":"D649","DOI":"10.1093\/nar\/gkx1132","volume":"46","author":"A Fabregat","year":"2018","unstructured":"Fabregat A, Jupe S, Matthews L, Sidiropoulos K, Gillespie M, Garapati P, et al. The Reactome Pathway Knowledgebase. Nucleic Acids Res. 2018;46:D649\u201355.","journal-title":"Nucleic Acids Res"},{"key":"760_CR50","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S1350-9462(01)00010-6","volume":"20","author":"GS Hageman","year":"2001","unstructured":"Hageman GS, Luthert PJ, Victor Chong NH, Johnson LV, Anderson DH, Mullins RF. An integrated hypothesis that considers drusen as biomarkers of immune-mediated processes at the RPE-Bruch\u2019s membrane interface in aging and age-related macular degeneration. Prog Retin Eye Res. 2001;20:705\u201332.","journal-title":"Prog Retin Eye Res"},{"key":"760_CR51","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1006\/exer.2001.1094","volume":"73","author":"LV Johnson","year":"2001","unstructured":"Johnson LV, Leitner WP, Staples MK, Anderson DH. Complement activation and inflammatory processes in Drusen formation and age related macular degeneration. Exp Eye Res. 2001;73:887\u201396.","journal-title":"Exp Eye Res"},{"key":"760_CR52","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.exer.2011.06.002","volume":"93","author":"SD Vogt","year":"2011","unstructured":"Vogt SD, Curcio CA, Wang L, Li CM, McGwin G Jr, Medeiros NE, et al. Retinal pigment epithelial expression of complement regulator CD46 is altered early in the course of geographic atrophy. Exp Eye Res. 2011;93:413\u201323.","journal-title":"Exp Eye Res"},{"key":"760_CR53","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1042\/bj2640581","volume":"264","author":"T Seya","year":"1989","unstructured":"Seya T, Atkinson JP. Functional properties of membrane cofactor protein of complement. Biochem J. 1989;264:581\u20138.","journal-title":"Biochem J"},{"key":"760_CR54","doi-asserted-by":"crossref","first-page":"4385","DOI":"10.1128\/JVI.78.9.4385-4388.2004","volume":"78","author":"R Cattaneo","year":"2004","unstructured":"Cattaneo R. Four viruses, two Bacteria, and one receptor: membrane cofactor protein (CD46) as pathogens\u2019 magnet. J Virol. 2004;78:4385\u20138.","journal-title":"J Virol"},{"key":"760_CR55","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1365-2249.2011.04400.x","volume":"164","author":"J Cardone","year":"2011","unstructured":"Cardone J, Le Friec G, Kemper C. CD46 in innate and adaptive immunity: an update. Clin Exp Immunol. 2011;164:301\u201311.","journal-title":"Clin Exp Immunol"},{"key":"760_CR56","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00439-017-1768-9","volume":"136","author":"IH Haralambieva","year":"2017","unstructured":"Haralambieva IH, Ovsyannikova IG, Kennedy RB, Larrabee BR, Zimmermann MT, Grill DE, et al. Genome-wide associations of CD46 and IFI44L genetic variants with neutralizing antibody response to measles vaccine. Hum Genet. 2017;136:421\u201335.","journal-title":"Hum Genet"},{"key":"760_CR57","volume-title":"Oculocutaneous Albinism Type 1 [Internet]. GeneReviews\u00ae","author":"RA Lewis","year":"1993","unstructured":"Lewis RA. Oculocutaneous Albinism Type 1 [Internet]. GeneReviews\u00ae. Seattle: University of Washington; 1993."},{"key":"760_CR58","doi-asserted-by":"crossref","unstructured":"Galv\u00e1n-Femen\u00eda I, Ob\u00f3n-Santacana M, Pi\u00f1eyro D, Guindo-Martinez M, Duran X, Carreras A, et al. Multitrait genome association analysis identifies new susceptibility genes for human anthropometric variation in the GCAT cohort. J Med Genet. 2018:765\u201378.","DOI":"10.1136\/jmedgenet-2018-105437"},{"key":"760_CR59","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1086\/522235","volume":"81","author":"RP Stokowski","year":"2007","unstructured":"Stokowski RP, Pant PVK, Dadd T, Fereday A, Hinds DA, Jarman C, et al. A Genomewide association study of skin pigmentation in a south Asian population. Am J Hum Genet Cell Press. 2007;81:1119\u201332.","journal-title":"Am J Hum Genet Cell Press"},{"key":"760_CR60","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1093\/hmg\/ddy422","volume":"28","author":"XR Gao","year":"2019","unstructured":"Gao XR, Huang H, Kim H. Genome-wide association analyses identify 139 loci associated with macular thickness in the UK biobank cohort. Hum Mol Genet. 2019;28:1162\u201372.","journal-title":"Hum Mol Genet"},{"key":"760_CR61","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1167\/iovs.18-25332","volume":"60","author":"C Brandl","year":"2019","unstructured":"Brandl C, Br\u00fccklmayer C, G\u00fcnther F, Zimmermann ME, K\u00fcchenhoff H, Helbig H, et al. Retinal layer thicknesses in early age-related macular degeneration: results from the German AugUR study. Invest Ophthalmol Vis Sci. 2019;60:1581\u201394.","journal-title":"Invest Ophthalmol Vis Sci"}],"container-title":["BMC Medical Genomics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-020-00760-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12920-020-00760-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12920-020-00760-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T19:57:11Z","timestamp":1629921431000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedgenomics.biomedcentral.com\/articles\/10.1186\/s12920-020-00760-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,26]]},"references-count":61,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["760"],"URL":"https:\/\/doi.org\/10.1186\/s12920-020-00760-7","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2019.12.20.883801","asserted-by":"object"}]},"ISSN":["1755-8794"],"issn-type":[{"value":"1755-8794","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,26]]},"assertion":[{"value":"16 October 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 August 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The Institutional Review Board (IRB) of the University of Utah was the umbrella IRB for all other studies contributing data to the International Age-related Macular Degeneration Genomics Consortium (IAMDGC), except for the Beaver Dam Eye Study (BDES). The University of Utah approved and certified each individual study ethic committee\u2019s conduct for the data used in this study. Data provided by BDES was approved by the IRB of the University of Wisconsin. Local ethics approval for data access to the studies deposited in dbGAP (WHI, ARIC and CHS) was granted by the IRB of the University of Regensburg. For all other studies, study participants obtained informed consent and local ethics committees approved the study protocols.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"M.S. receives funding from Pfizer Inc. for a project not related to this research. Retinal grading of the NICOLA study was supported by Novartis (for R.E.H) and Bayer (for Usha Chakravarthy, not a co-author). A.K.S. received financial and research support by Heidelberg Engineering, Novartis, Bayer Vital and Allergen without a link to the content of this work. I.M.H. received funding from Roche Diagnostics for a project not related to this research. None of the other authors have any conflicts of interest.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"120"}}