{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:06:55Z","timestamp":1783652815224,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,9,9]],"date-time":"2016-09-09T00:00:00Z","timestamp":1473379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genetic Epidemiology"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Previous studies have identified many genetic loci for refractive error and myopia. We aimed to investigate the effect of these loci on ocular biometry as a function of age in children, adolescents, and adults. The study population consisted of three age groups identified from the international CREAM consortium: 5,490 individuals aged &lt;10 years; 5,000 aged 10\u201325 years; and 16,274 aged &gt;25 years. All participants had undergone standard ophthalmic examination including measurements of axial length (<jats:italic>AL<\/jats:italic>) and corneal radius (<jats:italic>CR<\/jats:italic>). We examined the lead SNP at all 39 currently known genetic loci for refractive error identified from genome\u2010wide association studies (GWAS), as well as a combined genetic risk score (GRS). The beta coefficient for association between SNP genotype or GRS versus <jats:italic>AL<\/jats:italic>\/<jats:italic>CR<\/jats:italic> was compared across the three age groups, adjusting for age, sex, and principal components. Analyses were Bonferroni\u2010corrected. In the age group &lt;10 years, three loci (<jats:italic>GJD2, CHRNG, ZIC2<\/jats:italic>) were associated with <jats:italic>AL<\/jats:italic>\/<jats:italic>CR<\/jats:italic>. In the age group 10\u201325 years, four loci (<jats:italic>BMP2, KCNQ5, A2BP1, CACNA1D<\/jats:italic>) were associated; and in adults 20 loci were associated. Association with GRS increased with age; \u03b2 = 0.0016 per risk allele (<jats:italic>P<\/jats:italic> = 2 \u00d7 10<jats:sup>\u20138<\/jats:sup>) in &lt;10 years, 0.0033 (<jats:italic>P =<\/jats:italic> 5 \u00d7 10<jats:sup>\u201315<\/jats:sup>) in 10\u2010 to 25\u2010year\u2010olds, and 0.0048 (<jats:italic>P =<\/jats:italic> 1 \u00d7 10<jats:sup>\u201372<\/jats:sup>) in adults. Genes with strongest effects (<jats:italic>LAMA2<\/jats:italic>, <jats:italic>GJD2<\/jats:italic>) had an early effect that increased with age. Our results provide insights on the age span during which myopia genes exert their effect. These insights form the basis for understanding the mechanisms underlying high and pathological myopia.<\/jats:p>","DOI":"10.1002\/gepi.21999","type":"journal-article","created":{"date-parts":[[2016,9,9]],"date-time":"2016-09-09T17:46:10Z","timestamp":1473443170000},"page":"756-766","source":"Crossref","is-referenced-by-count":40,"title":["When do myopia genes have their effect? Comparison of genetic risks between children and adults"],"prefix":"10.1002","volume":"40","author":[{"given":"J. Willem L.","family":"Tideman","sequence":"first","affiliation":[{"name":"Department of Ophthalmology Erasmus Medical Center  Rotterdam The Netherlands"},{"name":"Department of Epidemiology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Fan","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute Singapore National Eye Centre  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan Roelof","family":"Polling","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Erasmus Medical Center  Rotterdam The Netherlands"},{"name":"Department of Orthoptics School of Applied Science Utrecht  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobo","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Statistical Science School of Mathematics &amp; Computational Science Sun Yat\u2010Sen University  Guangzhou GD China"},{"name":"SYSU\u2010CMU Shunde International Joint Research Institute  Guangzhou GD China"},{"name":"Southern China Research Center of Statistical Science Sun Yat\u2010Sen University  Guangzhou GD China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyhan","family":"Yazar","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science Lions Eye Institute University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Khawaja","sequence":"additional","affiliation":[{"name":"Department of Public Health and Primary Care Institute of Public Health University of Cambridge School of Clinical Medicine  Cambridge United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"H\u00f6hn","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Medical Center  Mainz Germany"},{"name":"Department of Ophthalmology Inselspital  Bern Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[{"name":"Statistical Genetics QIMR Berghofer Medical Research Institute  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent W.V.","family":"Jaddoe","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Yamashiro","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Kyoto University Graduate School of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munemitsu","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences Kyoto University Graduate School of Medicine  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aslihan","family":"Gerhold\u2010Ay","sequence":"additional","affiliation":[{"name":"Institute of Medical Biostatistics Epidemiology and Informatics University Medical Center Mainz  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Nickels","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Medical Center  Mainz Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Zeller","sequence":"additional","affiliation":[{"name":"Clinic for General and Interventional Cardiology University Heart Center Hamburg  Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingguang","family":"He","sequence":"additional","affiliation":[{"name":"Centre for Eye Research Australia University of Melbourne Royal Victorian Eye and Ear Hospital  Melbourne Australia"},{"name":"State Key Laboratory of Ophthalmology Zhongshan Ophthalmic Center Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thibaud","family":"Boutin","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh  Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goran","family":"Bencic","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Sisters of Mercy University Hospital  Zagreb Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Vitart","sequence":"additional","affiliation":[{"name":"Medical Research Council Human Genetics Unit Institute of Genetics and Molecular Medicine University of Edinburgh  Edinburgh United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Mackey","sequence":"additional","affiliation":[{"name":"Centre for Ophthalmology and Visual Science Lions Eye Institute University of Western Australia  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Foster","sequence":"additional","affiliation":[{"name":"NIHR Biomedical Research Centre Moorfields Eye Hospital NHS Foundation Trust &amp; UCL Institute of Ophthalmology  London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"MacGregor","sequence":"additional","affiliation":[{"name":"Statistical Genetics QIMR Berghofer Medical Research Institute  Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Williams","sequence":"additional","affiliation":[{"name":"School of Social and Community Medicine University of Bristol  Bristol England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seang Mei","family":"Saw","sequence":"additional","affiliation":[{"name":"Singapore Eye Research Institute Singapore National Eye Centre  Singapore"},{"name":"National University of Singapore Saw Swee Hock School of Public Health Singapore Eye Research Institute Singapore National Eye Centre  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A.","family":"Guggenheim","sequence":"additional","affiliation":[{"name":"School of Optometry &amp; Vision Sciences Cardiff University  Cardiff Wales"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline C. W.","family":"Klaver","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Erasmus Medical Center  Rotterdam The Netherlands"},{"name":"Department of Epidemiology Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the CREAM Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,9]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2012.06.009"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2010.05.004"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.04-0260"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.12.054"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2636"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9394(71)91092-0"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.03-1155"},{"issue":"1","key":"e_1_2_6_9_1","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1523\/JNEUROSCI.21-01-00230.2001","article-title":"Expression of neuronal connexin36 in AII amacrine cells of the mammalian retina","volume":"21","author":"Feigenspan A.","year":"2001","journal-title":"Journal of Neuroscience"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0420.2000.078005501.x"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2009.07.028"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9556"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1985.01050060045020"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.3.227"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043794"},{"issue":"3","key":"e_1_2_6_16_1","first-page":"220","article-title":"Axial length to corneal radius of curvature ratio and refractive errors","volume":"8","author":"Hashemi H.","year":"2013","journal-title":"Journal of Ophthalmic and Vision Research"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00684-6"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3319-04.2004"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(78)90736-9"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn923"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.211"},{"issue":"11","key":"e_1_2_6_22_1","first-page":"1550","article-title":"Acetylcholine receptors in the human retina","volume":"26","author":"Hutchins J. B.","year":"1985","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.664"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt522"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0101"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0902425106"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003299"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2003.03049.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/opo.12212"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2015.01.007"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1350-9462(02)00063-0"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755-3768.1992.tb08571.x"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/OPX.0b013e3182418213"},{"issue":"1","key":"e_1_2_6_34_1","first-page":"120","article-title":"Optical and structural development of the crystalline lens in childhood","volume":"39","author":"Mutti D. O.","year":"1998","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.813"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.survophthal.2010.07.003"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.2005.087999"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.663"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1001307"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0505"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2554"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1001\/archophthalmol.2009.303"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100378"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2011.10.007"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq340"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003442"},{"key":"e_1_2_6_47_1","first-page":"764","article-title":"Abundant L\u2010type calcium channel Ca(v)1.3 (alpha1D) subunit mRNA is detected in rod photoreceptors of the mouse retina via in situ hybridization","volume":"13","author":"Xiao H.","year":"2007","journal-title":"Molecular Vision"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.125.1.38"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006324-200303000-00012"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00185.2011"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2013.02.010"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-9917"}],"container-title":["Genetic Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgepi.21999","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fgepi.21999","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/gepi.21999","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T19:39:38Z","timestamp":1696361978000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/gepi.21999"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,9]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,12]]}},"alternative-id":["10.1002\/gepi.21999"],"URL":"https:\/\/doi.org\/10.1002\/gepi.21999","archive":["Portico"],"relation":{},"ISSN":["0741-0395","1098-2272"],"issn-type":[{"value":"0741-0395","type":"print"},{"value":"1098-2272","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,9]]}}}