{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:33:37Z","timestamp":1792805617390,"version":"4.5.0"},"reference-count":112,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Keratoconus is characterised by reduced rigidity of the cornea with distortion and focal thinning that causes blurred vision, however, the pathogenetic mechanisms are unknown. It can lead to severe visual morbidity in children and young adults and is a common indication for corneal transplantation worldwide. Here we report the first large scale genome-wide association study of keratoconus including 4,669 cases and 116,547 controls. We have identified significant association with 36 genomic loci that, for the first time, implicate both dysregulation of corneal collagen matrix integrity and cell differentiation pathways as primary disease-causing mechanisms. The results also suggest pleiotropy, with some disease mechanisms shared with other corneal diseases, such as Fuchs endothelial corneal dystrophy. The common variants associated with keratoconus explain 12.5% of the genetic variance, which shows potential for the future development of a diagnostic test to detect susceptibility to disease.<\/jats:p>","DOI":"10.1038\/s42003-021-01784-0","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T06:07:32Z","timestamp":1614578852000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0038-6770","authenticated-orcid":false,"given":"Alison J.","family":"Hardcastle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7834-8486","authenticated-orcid":false,"given":"Petra","family":"Liskova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yelena","family":"Bykhovskaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1940-0007","authenticated-orcid":false,"given":"Bennet J.","family":"McComish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1816-6151","authenticated-orcid":false,"given":"Alice E.","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5143-2562","authenticated-orcid":false,"given":"Chris F.","family":"Inglehearn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5037-3572","authenticated-orcid":false,"given":"Xiaohui","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9839-8667","authenticated-orcid":false,"given":"H\u00e9l\u00e8ne","family":"Choquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Habeeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sionne E. M.","family":"Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1945-7209","authenticated-orcid":false,"given":"Srujana","family":"Sahebjada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1782-4711","authenticated-orcid":false,"given":"Nikolas","family":"Pontikos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla E. Rojas","family":"Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6802-8585","authenticated-orcid":false,"given":"Anthony P.","family":"Khawaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-3788","authenticated-orcid":false,"given":"Manir","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lubica","family":"Dudakova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavlina","family":"Skalicka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart T. H.","family":"Van Dooren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette J. M.","family":"Geerards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3872-5643","authenticated-orcid":false,"given":"Christoph W.","family":"Haudum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4931-7327","authenticated-orcid":false,"given":"Valeria Lo","family":"Faro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abi","family":"Tenen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2432-0810","authenticated-orcid":false,"given":"Mark J.","family":"Simcoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karina","family":"Patasova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3570-3921","authenticated-orcid":false,"given":"Darioush","family":"Yarrand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salina","family":"Siddiqui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aine","family":"Rice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1484-192X","authenticated-orcid":false,"given":"Layal Abi","family":"Farraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yii-Der Ida","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jugnoo S.","family":"Rahi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald M.","family":"Krauss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Theusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jac C.","family":"Charlesworth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta","family":"Szczotka-Flynn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmel","family":"Toomes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magda A.","family":"Meester-Smoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea J.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul A.","family":"Mitchell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2756-4370","authenticated-orcid":false,"given":"Kent D.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald B.","family":"Melles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Aldave","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Mills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsie","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Daniell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9491-4898","authenticated-orcid":false,"given":"Jie Jin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7191-1723","authenticated-orcid":false,"given":"Jerome I.","family":"Rotter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5123-5999","authenticated-orcid":false,"given":"Alex W.","family":"Hewitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6731-8142","authenticated-orcid":false,"given":"Stuart","family":"MacGregor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2355-5258","authenticated-orcid":false,"given":"Caroline C. W.","family":"Klaver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1780-5281","authenticated-orcid":false,"given":"Wishal D.","family":"Ramdas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie E.","family":"Craig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudha K.","family":"Iyengar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"O\u2019Brart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5829-8191","authenticated-orcid":false,"given":"Eric","family":"Jorgenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1305-3502","authenticated-orcid":false,"given":"Paul N.","family":"Baird","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaron S.","family":"Rabinowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8217-1249","authenticated-orcid":false,"given":"Kathryn P.","family":"Burdon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3227-2620","authenticated-orcid":false,"given":"Chris J.","family":"Hammond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8192-5192","authenticated-orcid":false,"given":"Stephen J.","family":"Tuft","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5752-2510","authenticated-orcid":false,"given":"Pirro G.","family":"Hysi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,3,1]]},"reference":[{"key":"1784_CR1","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.ajo.2016.12.015","volume":"175","author":"DA Godefrooij","year":"2017","unstructured":"Godefrooij, D. A., de Wit, G. A., Uiterwaal, C. S., Imhof, S. M. & Wisse, R. P. Age-specific incidence and prevalence of keratoconus: a nationwide registration study. Am. J. Ophthalmol. 175, 169\u2013172 (2017).","journal-title":"Am. J. Ophthalmol."},{"key":"1784_CR2","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1111\/j.1600-0420.2007.00981.x","volume":"85","author":"K Nielsen","year":"2007","unstructured":"Nielsen, K., Hjortdal, J., Aagaard Nohr, E. & Ehlers, N. Incidence and prevalence of keratoconus in Denmark. Acta Ophthalmol. Scand. 85, 890\u2013892 (2007).","journal-title":"Acta Ophthalmol. Scand."},{"key":"1784_CR3","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.ajo.2004.04.031","volume":"138","author":"SM Kymes","year":"2004","unstructured":"Kymes, S. M., Walline, J. J., Zadnik, K. & Gordon, M. O. Collaborative longitudinal evaluation of keratoconus study, g. Quality of life in keratoconus. Am. J. Ophthalmol. 138, 527\u2013535 (2004).","journal-title":"Am. J. Ophthalmol."},{"key":"1784_CR4","doi-asserted-by":"crossref","unstructured":"Bak-Nielsen, S., Ramlau-Hansen, C. H., Ivarsen, A., Plana-Ripoll, O. & Hjortdal, J. A nationwide population-based study of social demographic factors, associated diseases and mortality of keratoconus patients in Denmark from 1977 to 2015. Acta Ophthalmol. 97, 497\u2013504 (2018).","DOI":"10.1111\/aos.13961"},{"key":"1784_CR5","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1016\/j.survophthal.2017.06.009","volume":"62","author":"V Mas Tur","year":"2017","unstructured":"Mas Tur, V., MacGregor, C., Jayaswal, R., O\u2019Brart, D. & Maycock, N. A review of keratoconus: diagnosis, pathophysiology, and genetics. Surv. Ophthalmol. 62, 770\u2013783 (2017).","journal-title":"Surv. Ophthalmol."},{"key":"1784_CR6","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1001\/jamaophthalmol.2015.4776","volume":"134","author":"P Gain","year":"2016","unstructured":"Gain, P. et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 134, 167\u2013173 (2016).","journal-title":"JAMA Ophthalmol."},{"key":"1784_CR7","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.1097\/TP.0000000000001281","volume":"101","author":"M Matthaei","year":"2017","unstructured":"Matthaei, M. et al. Changing indications in penetrating keratoplasty: a systematic review of 34 years of global reporting. Transplantation 101, 1387\u20131399 (2017).","journal-title":"Transplantation"},{"key":"1784_CR8","doi-asserted-by":"publisher","unstructured":"Chan, E. et al. Prevalence of keratoconus based on Scheimpflug imaging: The Raine Study. Ophthalmology https:\/\/doi.org\/10.1016\/j.ophtha.2020.08.020 (2020).","DOI":"10.1016\/j.ophtha.2020.08.020"},{"key":"1784_CR9","doi-asserted-by":"publisher","first-page":"385","DOI":"10.3109\/09286586.2013.848458","volume":"20","author":"H Hashemi","year":"2013","unstructured":"Hashemi, H., Khabazkhoob, M. & Fotouhi, A. Topographic keratoconus is not rare in an Iranian population: the Tehran Eye Study. Ophthalmic Epidemiol. 20, 385\u2013391 (2013).","journal-title":"Ophthalmic Epidemiol."},{"key":"1784_CR10","doi-asserted-by":"publisher","first-page":"1382","DOI":"10.1097\/ICO.0000000000002054","volume":"38","author":"AT Papali\u2019i-Curtin","year":"2019","unstructured":"Papali\u2019i-Curtin, A. T. et al. Keratoconus prevalence among high school students in New Zealand. Cornea 38, 1382\u20131389 (2019).","journal-title":"Cornea"},{"key":"1784_CR11","doi-asserted-by":"publisher","first-page":"e482","DOI":"10.1111\/j.1755-3768.2012.02448.x","volume":"90","author":"SJ Tuft","year":"2012","unstructured":"Tuft, S. J. et al. Keratoconus in 18 pairs of twins. Acta Ophthalmol. 90, e482\u2013e486 (2012).","journal-title":"Acta Ophthalmol."},{"key":"1784_CR12","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/1096-8628(20000828)93:5<403::AID-AJMG11>3.0.CO;2-A","volume":"93","author":"Y Wang","year":"2000","unstructured":"Wang, Y., Rabinowitz, Y. S., Rotter, J. I. & Yang, H. Genetic epidemiological study of keratoconus: evidence for major gene determination. Am. J. Med. Genet. 93, 403\u2013409 (2000).","journal-title":"Am. J. Med. Genet."},{"key":"1784_CR13","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.ophtha.2015.10.035","volume":"123","author":"MA Woodward","year":"2016","unstructured":"Woodward, M. A., Blachley, T. S. & Stein, J. D. The association between sociodemographic factors, common systemic diseases, and keratoconus: an analysis of a Nationwide Heath Care Claims Database. Ophthalmology 123, 457\u201365 e2 (2016).","journal-title":"Ophthalmology"},{"key":"1784_CR14","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1167\/iovs.08-2382","volume":"50","author":"L Bisceglia","year":"2009","unstructured":"Bisceglia, L. et al. Linkage analysis in keratoconus: replication of locus 5q21.2 and identification of other suggestive Loci. Invest. Ophthalmol. Vis. Sci. 50, 1081\u20131086 (2009).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"1784_CR15","doi-asserted-by":"publisher","first-page":"8514","DOI":"10.1167\/iovs.11-8261","volume":"52","author":"KP Burdon","year":"2011","unstructured":"Burdon, K. P. et al. Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus. Invest Ophthalmol. Vis. Sci. 52, 8514\u20138519 (2011).","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"1784_CR16","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03646-6","volume":"9","author":"AI Iglesias","year":"2018","unstructured":"Iglesias, A. I. et al. Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. Nat. Commun. 9, 1864 (2018).","journal-title":"Nat. Commun."},{"key":"1784_CR17","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/ng.2506","volume":"45","author":"Y Lu","year":"2013","unstructured":"Lu, Y. et al. Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus. Nat. Genet. 45, 155\u2013163 (2013).","journal-title":"Nat. Genet."},{"key":"1784_CR18","unstructured":"Dyrlund, T. et al. Human cornea proteome: identification and quantitation of the proteins of the three main layers including epithelium, stroma and endothelium. Investigative Ophthalmol. Visual Sci. 54 (2013)."},{"key":"1784_CR19","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1097\/01.GIM.0000170772.41860.54","volume":"7","author":"YG Tang","year":"2005","unstructured":"Tang, Y. G. et al. Genomewide linkage scan in a multigeneration Caucasian pedigree identifies a novel locus for keratoconus on chromosome 5q14.3-q21.1. Genet. Med. 7, 397\u2013405 (2005).","journal-title":"Genet. Med."},{"key":"1784_CR20","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1038\/s42003-020-1037-7","volume":"3","author":"H Choquet","year":"2020","unstructured":"Choquet, H. et al. A multiethnic genome-wide analysis of 44,039 individuals identifies 41 new loci associated with central corneal thickness. Commun. Biol. 3, 301 (2020).","journal-title":"Commun. Biol."},{"key":"1784_CR21","doi-asserted-by":"publisher","first-page":"e0172365","DOI":"10.1371\/journal.pone.0172365","volume":"12","author":"P Liskova","year":"2017","unstructured":"Liskova, P., Dudakova, L., Krepelova, A., Klema, J. & Hysi, P. G. Replication of SNP associations with keratoconus in a Czech cohort. PLoS ONE 12, e0172365 (2017).","journal-title":"PLoS ONE"},{"key":"1784_CR22","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1111\/j.0006-341X.1999.00997.x","volume":"55","author":"B Devlin","year":"1999","unstructured":"Devlin, B. & Roeder, K. Genomic control for association studies. Biometrics 55, 997\u20131004 (1999).","journal-title":"Biometrics"},{"key":"1784_CR23","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1093\/hmg\/ddr460","volume":"21","author":"X Li","year":"2012","unstructured":"Li, X. et al. A genome-wide association study identifies a potential novel gene locus for keratoconus, one of the commonest causes for corneal transplantation in developed countries. Hum. Mol. Genet 21, 421\u2013429 (2012).","journal-title":"Hum. Mol. Genet"},{"key":"1784_CR24","doi-asserted-by":"crossref","unstructured":"McComish, B. J. et al. Association of Genetic Variation With Keratoconus. JAMA Ophthalmol. 38, 174\u2013181 (2019).","DOI":"10.1001\/jamaophthalmol.2019.5293"},{"key":"1784_CR25","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/ng.3211","volume":"47","author":"BK Bulik-Sullivan","year":"2015","unstructured":"Bulik-Sullivan, B. K. et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291\u2013295 (2015).","journal-title":"Nat. Genet."},{"key":"1784_CR26","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1016\/j.addr.2003.08.002","volume":"55","author":"K Gelse","year":"2003","unstructured":"Gelse, K., Poschl, E. & Aigner, T. Collagens-structure, function, and biosynthesis. Adv. Drug Deliv. Rev. 55, 1531\u20131546 (2003).","journal-title":"Adv. Drug Deliv. Rev."},{"key":"1784_CR27","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1002\/jcb.10290","volume":"87","author":"BB Young","year":"2002","unstructured":"Young, B. B., Zhang, G., Koch, M. & Birk, D. E. The roles of types XII and XIV collagen in fibrillogenesis and matrix assembly in the developing cornea. J. Cell Biochem. 87, 208\u2013220 (2002).","journal-title":"J. Cell Biochem."},{"key":"1784_CR28","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.exer.2018.07.024","volume":"177","author":"EM Feneck","year":"2018","unstructured":"Feneck, E. M., Lewis, P. N., Ralphs, J. & Meek, K. M. A comparative study of the elastic fibre system within the mouse and human cornea. Exp. Eye Res. 177, 35\u201344 (2018).","journal-title":"Exp. Eye Res."},{"key":"1784_CR29","doi-asserted-by":"publisher","first-page":"4096","DOI":"10.1242\/jcs.091363","volume":"124","author":"M Sun","year":"2011","unstructured":"Sun, M. et al. Collagen V is a dominant regulator of collagen fibrillogenesis: dysfunctional regulation of structure and function in a corneal-stroma-specific Col5a1-null mouse model. J. Cell Sci. 124, 4096\u20134105 (2011).","journal-title":"J. Cell Sci."},{"key":"1784_CR30","first-page":"547","volume":"60","author":"A De Paepe","year":"1997","unstructured":"De Paepe, A., Nuytinck, L., Hausser, I., Anton-Lamprecht, I. & Naeyaert, J. M. Mutations in the COL5A1 gene are causal in the Ehlers-Danlos syndromes I and II. Am. J. Hum. Genet 60, 547\u2013554 (1997).","journal-title":"Am. J. Hum. Genet"},{"key":"1784_CR31","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1111\/j.1399-0004.2011.01758.x","volume":"82","author":"M Klaassens","year":"2012","unstructured":"Klaassens, M. et al. Ehlers-Danlos arthrochalasia type (VIIA-B)-expanding the phenotype: from prenatal life through adulthood. Clin. Genet. 82, 121\u2013130 (2012).","journal-title":"Clin. Genet."},{"key":"1784_CR32","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.1093\/hmg\/ddt627","volume":"23","author":"Y Zou","year":"2014","unstructured":"Zou, Y. et al. Recessive and dominant mutations in COL12A1 cause a novel EDS\/myopathy overlap syndrome in humans and mice. Hum. Mol. Genet. 23, 2339\u20132352 (2014).","journal-title":"Hum. Mol. Genet."},{"key":"1784_CR33","doi-asserted-by":"crossref","unstructured":"Delbaere, S. et al. Novel defects in collagen XII and VI expand the mixed myopathy\/Ehlers-Danlos syndrome spectrum and lead to variant-specific alterations in the extracellular matrix. Genet. Med. 22, 112\u2013123 (2019).","DOI":"10.1038\/s41436-019-0599-6"},{"key":"1784_CR34","doi-asserted-by":"publisher","first-page":"2304","DOI":"10.1007\/s00018-006-6149-9","volume":"63","author":"HA Lucero","year":"2006","unstructured":"Lucero, H. A. & Kagan, H. M. Lysyl oxidase: an oxidative enzyme and effector of cell function. Cell Mol. Life Sci. 63, 2304\u20132316 (2006).","journal-title":"Cell Mol. Life Sci."},{"key":"1784_CR35","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/j.1432-1033.1993.tb18017.x","volume":"215","author":"A Kern","year":"1993","unstructured":"Kern, A., Eble, J., Golbik, R. & Kuhn, K. Interaction of type IV collagen with the isolated integrins alpha 1 beta 1 and alpha 2 beta 1. Eur. J. Biochem. 215, 151\u2013159 (1993).","journal-title":"Eur. J. Biochem."},{"key":"1784_CR36","doi-asserted-by":"publisher","first-page":"37377","DOI":"10.1074\/jbc.M206286200","volume":"277","author":"T Velling","year":"2002","unstructured":"Velling, T., Risteli, J., Wennerberg, K., Mosher, D. F. & Johansson, S. Polymerization of type I and III collagens is dependent on fibronectin and enhanced by integrins alpha(11)beta(1) and alpha(2)beta(1). J. Biol. Chem. 277, 37377\u201337381 (2002).","journal-title":"J. Biol. Chem."},{"key":"1784_CR37","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.exer.2011.01.008","volume":"92","author":"R Joseph","year":"2011","unstructured":"Joseph, R., Srivastava, O. P. & Pfister, R. R. Differential epithelial and stromal protein profiles in keratoconus and normal human corneas. Exp. Eye Res. 92, 282\u2013298 (2011).","journal-title":"Exp. Eye Res."},{"key":"1784_CR38","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.semcdb.2007.09.015","volume":"19","author":"JV Jester","year":"2008","unstructured":"Jester, J. V. Corneal crystallins and the development of cellular transparency. Semin Cell Dev. Biol. 19, 82\u201393 (2008).","journal-title":"Semin Cell Dev. Biol."},{"key":"1784_CR39","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/j.exer.2006.05.011","volume":"83","author":"Y Pei","year":"2006","unstructured":"Pei, Y., Reins, R. Y. & McDermott, A. M. Aldehyde dehydrogenase (ALDH) 3A1 expression by the human keratocyte and its repair phenotypes. Exp. Eye Res. 83, 1063\u20131073 (2006).","journal-title":"Exp. Eye Res."},{"key":"1784_CR40","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.brainresbull.2009.08.017","volume":"81","author":"D Stagos","year":"2010","unstructured":"Stagos, D., Chen, Y., Cantore, M., Jester, J. V. & Vasiliou, V. Corneal aldehyde dehydrogenases: multiple functions and novel nuclear localization. Brain Res. Bull. 81, 211\u2013218 (2010).","journal-title":"Brain Res. Bull."},{"key":"1784_CR41","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/S0009-2797(00)00270-2","volume":"130-132","author":"AJ Townsend","year":"2001","unstructured":"Townsend, A. J. et al. Selective protection by stably transfected human ALDH3A1 (but not human ALDH1A1) against toxicity of aliphatic aldehydes in V79 cells. Chem. Biol. Interact. 130-132, 261\u2013273 (2001).","journal-title":"Chem. Biol. Interact."},{"key":"1784_CR42","doi-asserted-by":"publisher","first-page":"e0146433","DOI":"10.1371\/journal.pone.0146433","volume":"11","author":"V Koppaka","year":"2016","unstructured":"Koppaka, V. et al. ALDH3A1 plays a functional role in maintenance of corneal epithelial homeostasis. PLoS One 11, e0146433 (2016).","journal-title":"PLoS One"},{"key":"1784_CR43","doi-asserted-by":"publisher","first-page":"e44771","DOI":"10.1371\/journal.pone.0044771","volume":"7","author":"D Kenchegowda","year":"2012","unstructured":"Kenchegowda, D., Harvey, S. A., Swamynathan, S., Lathrop, K. L. & Swamynathan, S. K. Critical role of Klf5 in regulating gene expression during post-eyelid opening maturation of mouse corneas. PLoS ONE 7, e44771 (2012).","journal-title":"PLoS ONE"},{"key":"1784_CR44","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1002\/iub.1233","volume":"65","author":"SM Diakiw","year":"2013","unstructured":"Diakiw, S. M., D\u2019Andrea, R. J. & Brown, A. L. The double life of KLF5: Opposing roles in regulation of gene-expression, cellular function, and transformation. IUBMB Life 65, 999\u20131011 (2013).","journal-title":"IUBMB Life"},{"key":"1784_CR45","doi-asserted-by":"publisher","first-page":"2691","DOI":"10.1007\/s00018-009-0045-z","volume":"66","author":"JT Dong","year":"2009","unstructured":"Dong, J. T. & Chen, C. Essential role of KLF5 transcription factor in cell proliferation and differentiation and its implications for human diseases. Cell Mol. Life Sci. 66, 2691\u20132706 (2009).","journal-title":"Cell Mol. Life Sci."},{"key":"1784_CR46","doi-asserted-by":"publisher","first-page":"34304","DOI":"10.1074\/jbc.M113.504399","volume":"288","author":"DN Stephens","year":"2013","unstructured":"Stephens, D. N. et al. The Ets transcription factor EHF as a regulator of cornea epithelial cell identity. J. Biol. Chem. 288, 34304\u201334324 (2013).","journal-title":"J. Biol. Chem."},{"key":"1784_CR47","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1128\/MCB.00846-06","volume":"27","author":"SK Swamynathan","year":"2007","unstructured":"Swamynathan, S. K. et al. Conditional deletion of the mouse Klf4 gene results in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells. Mol. Cell Biol. 27, 182\u2013194 (2007).","journal-title":"Mol. Cell Biol."},{"key":"1784_CR48","doi-asserted-by":"publisher","first-page":"4689","DOI":"10.1167\/iovs.02-0999","volume":"44","author":"A Joseph","year":"2003","unstructured":"Joseph, A. et al. Expression of CD34 and L-selectin on human corneal keratocytes. Invest Ophthalmol. Vis. Sci. 44, 4689\u20134692 (2003).","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"1784_CR49","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1016\/S0014-4827(02)00015-0","volume":"282","author":"RA Evans","year":"2003","unstructured":"Evans, R. A., Tian, Y. C., Steadman, R. & Phillips, A. O. TGF-beta1-mediated fibroblast-myofibroblast terminal differentiation-the role of Smad proteins. Exp. Cell Res. 282, 90\u2013100 (2003).","journal-title":"Exp. Cell Res."},{"key":"1784_CR50","first-page":"97","volume":"62","author":"B Li","year":"2016","unstructured":"Li, B. et al. Knockdown of eIF3a ameliorates cardiac fibrosis by inhibiting the TGF-beta1\/Smad3 signaling pathway. Cell Mol. Biol. (Noisy-le.-Gd.) 62, 97\u2013101 (2016).","journal-title":"Cell Mol. Biol. (Noisy-le.-Gd.)"},{"key":"1784_CR51","doi-asserted-by":"publisher","first-page":"1889","DOI":"10.1016\/j.yexcr.2009.03.009","volume":"315","author":"Z Dong","year":"2009","unstructured":"Dong, Z. et al. Role of eIF3a in regulating cell cycle progression. Exp. Cell Res. 315, 1889\u20131894 (2009).","journal-title":"Exp. Cell Res."},{"key":"1784_CR52","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1007\/s00018-018-2766-3","volume":"75","author":"E De Keuckelaere","year":"2018","unstructured":"De Keuckelaere, E., Hulpiau, P., Saeys, Y., Berx, G. & van Roy, F. Nanos genes and their role in development and beyond. Cell Mol. Life Sci. 75, 1929\u20131946 (2018).","journal-title":"Cell Mol. Life Sci."},{"key":"1784_CR53","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1002\/stem.1565","volume":"32","author":"S Saoncella","year":"2014","unstructured":"Saoncella, S. et al. Nuclear Akt2 opposes limbal keratinocyte stem cell self-renewal by repressing a FOXO-mTORC1 signaling pathway. Stem Cells 32, 754\u2013769 (2014).","journal-title":"Stem Cells"},{"key":"1784_CR54","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1126\/science.1207194","volume":"334","author":"D Noordermeer","year":"2011","unstructured":"Noordermeer, D. et al. The dynamic architecture of Hox gene clusters. Science 334, 222\u2013225 (2011).","journal-title":"Science"},{"key":"1784_CR55","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14898","volume":"8","author":"NA Afshari","year":"2017","unstructured":"Afshari, N. A. et al. Genome-wide association study identifies three novel loci in Fuchs endothelial corneal dystrophy. Nat. Commun. 8, 14898 (2017).","journal-title":"Nat. Commun."},{"key":"1784_CR56","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1126\/science.1262110","volume":"348","author":"GT Consortium","year":"2015","unstructured":"Consortium, G. T. Human genomics. The Genotype-Tissue Expression (GTEx) pilot analysis: multitissue gene regulation in humans. Science 348, 648\u2013660 (2015).","journal-title":"Science"},{"key":"1784_CR57","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.exer.2016.11.021","volume":"167","author":"MU Carnes","year":"2018","unstructured":"Carnes, M. U., Allingham, R. R., Ashley-Koch, A. & Hauser, M. A. Transcriptome analysis of adult and fetal trabecular meshwork, cornea, and ciliary body tissues by RNA sequencing. Exp. Eye Res. 167, 91\u201399 (2018).","journal-title":"Exp. Eye Res."},{"key":"1784_CR58","doi-asserted-by":"publisher","first-page":"2717","DOI":"10.1167\/iovs.18-24267","volume":"59","author":"ML Khaled","year":"2018","unstructured":"Khaled, M. L. et al. Differential expression of coding and long noncoding RNAs in keratoconus-affected corneas. Invest Ophthalmol. Vis. Sci. 59, 2717\u20132728 (2018).","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"1784_CR59","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1038\/s41588-018-0081-4","volume":"50","author":"HK Finucane","year":"2018","unstructured":"Finucane, H. K. et al. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nat. Genet. 50, 621\u2013629 (2018).","journal-title":"Nat. Genet."},{"key":"1784_CR60","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/ng.3538","volume":"48","author":"Z Zhu","year":"2016","unstructured":"Zhu, Z. et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat. Genet. 48, 481\u2013487 (2016).","journal-title":"Nat. Genet."},{"key":"1784_CR61","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","volume":"126","author":"K Takahashi","year":"2006","unstructured":"Takahashi, K. & Yamanaka, S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126, 663\u2013676 (2006).","journal-title":"Cell"},{"key":"1784_CR62","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1167\/iovs.18-26423","volume":"60","author":"A Tiwari","year":"2019","unstructured":"Tiwari, A. et al. KLF4 regulates corneal epithelial cell cycle progression by suppressing canonical TGF-beta signaling and upregulating CDK inhibitors P16 and P27. Invest Ophthalmol. Vis. Sci. 60, 731\u2013740 (2019).","journal-title":"Invest Ophthalmol. Vis. Sci."},{"key":"1784_CR63","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1038\/eye.2015.63","volume":"29","author":"V Galvis","year":"2015","unstructured":"Galvis, V. et al. Keratoconus: an inflammatory disorder? Eye (Lond.) 29, 843\u2013859 (2015).","journal-title":"Eye (Lond.)"},{"key":"1784_CR64","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1080\/08820538.2018.1539183","volume":"33","author":"M Bohac","year":"2018","unstructured":"Bohac, M. et al. Incidence and clinical characteristics of post LASIK ectasia: a review of over 30,000 LASIK cases. Semin. Ophthalmol. 33, 869\u2013877 (2018).","journal-title":"Semin. Ophthalmol."},{"key":"1784_CR65","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.ophtha.2019.02.029","volume":"126","author":"AC Ferdi","year":"2019","unstructured":"Ferdi, A. C. et al. Keratoconus natural progression: a systematic review and meta-analysis of 11 529 Eyes. Ophthalmology 126, 935\u2013945 (2019).","journal-title":"Ophthalmology"},{"key":"1784_CR66","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.lab.2006.01.005","volume":"147","author":"AJ Richardson","year":"2006","unstructured":"Richardson, A. J., Narendran, N., Guymer, R. H., Vu, H. & Baird, P. N. Blood storage at 4 degrees C-factors involved in DNA yield and quality. J. Lab Clin. Med. 147, 290\u2013294 (2006).","journal-title":"J. Lab Clin. Med."},{"key":"1784_CR67","doi-asserted-by":"publisher","first-page":"e84067","DOI":"10.1371\/journal.pone.0084067","volume":"9","author":"S Sahebjada","year":"2014","unstructured":"Sahebjada, S. et al. Association of the hepatocyte growth factor gene with keratoconus in an Australian population. PLoS ONE 9, e84067 (2014).","journal-title":"PLoS ONE"},{"key":"1784_CR68","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203\u2013209 (2018).","journal-title":"Nature"},{"key":"1784_CR69","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1016\/j.amjcard.2005.09.134","volume":"97","author":"JA Simon","year":"2006","unstructured":"Simon, J. A. et al. Phenotypic predictors of response to simvastatin therapy among African-Americans and Caucasians: the Cholesterol and Pharmacogenetics (CAP) Study. Am. J. Cardiol. 97, 843\u2013850 (2006).","journal-title":"Am. J. Cardiol."},{"key":"1784_CR70","doi-asserted-by":"publisher","first-page":"371","DOI":"10.3928\/1081-597X-19950901-14","volume":"11","author":"YS Rabinowitz","year":"1995","unstructured":"Rabinowitz, Y. S. Videokeratographic indices to aid in screening for keratoconus. J. Refract. Surg. 11, 371\u2013379 (1995).","journal-title":"J. Refract. Surg."},{"key":"1784_CR71","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1038\/ng.3656","volume":"48","author":"S Das","year":"2016","unstructured":"Das, S. et al. Next-generation genotype imputation service and methods. Nat. Genet. 48, 1284\u20131287 (2016).","journal-title":"Nat. Genet."},{"key":"1784_CR72","doi-asserted-by":"publisher","first-page":"1279","DOI":"10.1038\/ng.3643","volume":"48","author":"S McCarthy","year":"2016","unstructured":"McCarthy, S. et al. A reference panel of 64,976 haplotypes for genotype imputation. Nat. Genet. 48, 1279\u20131283 (2016).","journal-title":"Nat. Genet."},{"key":"1784_CR73","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1086\/519795","volume":"81","author":"S Purcell","year":"2007","unstructured":"Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559\u2013575 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"1784_CR74","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/ng1847","volume":"38","author":"AL Price","year":"2006","unstructured":"Price, A. L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904\u2013909 (2006).","journal-title":"Nat. Genet."},{"key":"1784_CR75","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1093\/bioinformatics\/btw079","volume":"32","author":"X Zhan","year":"2016","unstructured":"Zhan, X., Hu, Y., Li, B., Abecasis, G. R. & Liu, D. J. RVTESTS: an efficient and comprehensive tool for rare variant association analysis using sequence data. Bioinformatics 32, 1423\u20131426 (2016).","journal-title":"Bioinformatics"},{"key":"1784_CR76","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s00439-008-0555-z","volume":"124","author":"KP Burdon","year":"2008","unstructured":"Burdon, K. P. et al. Apparent autosomal dominant keratoconus in a large Australian pedigree accounted for by digenic inheritance of two novel loci. Hum. Genet. 124, 379\u2013386 (2008).","journal-title":"Hum. Genet."},{"key":"1784_CR77","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.ajo.2014.09.020","volume":"159","author":"KP Burdon","year":"2015","unstructured":"Burdon, K. P. et al. Association of open-angle glaucoma loci with incident glaucoma in the Blue Mountains Eye Study. Am. J. Ophthalmol. 159, 31\u201336.e1 (2015).","journal-title":"Am. J. Ophthalmol."},{"key":"1784_CR78","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.ajo.2012.04.023","volume":"154","author":"DP Dimasi","year":"2012","unstructured":"Dimasi, D. P. et al. Genetic investigation into the endophenotypic status of central corneal thickness and optic disc parameters in relation to open-angle glaucoma. Am. J. Ophthalmol. 154, 833\u2013842.e2 (2012).","journal-title":"Am. J. Ophthalmol."},{"key":"1784_CR79","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1038\/ng.3448","volume":"48","author":"LG Fritsche","year":"2016","unstructured":"Fritsche, L. G. et al. A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants. Nat. Genet. 48, 134\u2013143 (2016).","journal-title":"Nat. Genet."},{"key":"1784_CR80","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1038\/nprot.2010.116","volume":"5","author":"CA Anderson","year":"2010","unstructured":"Anderson, C. A. et al. Data quality control in genetic case-control association studies. Nat. Protoc. 5, 1564\u20131573 (2010).","journal-title":"Nat. Protoc."},{"key":"1784_CR81","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1038\/ng.3679","volume":"48","author":"P-R Loh","year":"2016","unstructured":"Loh, P.-R. et al. Reference-based phasing using the Haplotype Reference Consortium panel. Nat. Genet. 48, 1443\u20131448 (2016).","journal-title":"Nat. Genet."},{"key":"1784_CR82","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature15393","volume":"526","author":"A Auton","year":"2015","unstructured":"Auton, A. et al. A global reference for human genetic variation. Nature 526, 68\u201374 (2015).","journal-title":"Nature"},{"key":"1784_CR83","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8","volume":"4","author":"CC Chang","year":"2015","unstructured":"Chang, C. C. et al. Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4, 7 (2015).","journal-title":"Gigascience"},{"key":"1784_CR84","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1534\/genetics.115.178616","volume":"200","author":"Y Banda","year":"2015","unstructured":"Banda, Y. et al. Characterizing race\/ethnicity and genetic ancestry for 100,000 subjects in the genetic epidemiology research on adult health and aging (GERA) cohort. Genetics 200, 1285\u20131295 (2015).","journal-title":"Genetics"},{"key":"1784_CR85","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1534\/genetics.115.178905","volume":"200","author":"MN Kvale","year":"2015","unstructured":"Kvale, M. N. et al. Genotyping informatics and quality control for 100,000 subjects in the genetic epidemiology research on adult health and aging (GERA) cohort. Genetics 200, 1051\u20131060 (2015).","journal-title":"Genetics"},{"key":"1784_CR86","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.ygeno.2011.04.005","volume":"98","author":"TJ Hoffmann","year":"2011","unstructured":"Hoffmann, T. J. et al. Next generation genome-wide association tool: design and coverage of a high-throughput European-optimized SNP array. Genomics 98, 79\u201389 (2011).","journal-title":"Genomics"},{"key":"1784_CR87","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.ygeno.2011.08.007","volume":"98","author":"TJ Hoffmann","year":"2011","unstructured":"Hoffmann, T. J. et al. Design and coverage of high throughput genotyping arrays optimized for individuals of East Asian, African American, and Latino race\/ethnicity using imputation and a novel hybrid SNP selection algorithm. Genomics 98, 422\u2013430 (2011).","journal-title":"Genomics"},{"key":"1784_CR88","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nmeth.1785","volume":"9","author":"O Delaneau","year":"2012","unstructured":"Delaneau, O., Marchini, J. & Zagury, J. F. A linear complexity phasing method for thousands of genomes. Nat. Methods 9, 179\u2013181 (2012).","journal-title":"Nat. Methods"},{"key":"1784_CR89","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1038\/ng.2354","volume":"44","author":"B Howie","year":"2012","unstructured":"Howie, B., Fuchsberger, C., Stephens, M., Marchini, J. & Abecasis, G. R. Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat. Genet. 44, 955\u2013959 (2012).","journal-title":"Nat. Genet."},{"key":"1784_CR90","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1534\/g3.111.001198","volume":"1","author":"B Howie","year":"2011","unstructured":"Howie, B., Marchini, J. & Stephens, M. Genotype imputation with thousands of genomes. G3 1, 457\u2013470 (2011).","journal-title":"G3"},{"key":"1784_CR91","doi-asserted-by":"publisher","first-page":"e1000529","DOI":"10.1371\/journal.pgen.1000529","volume":"5","author":"BN Howie","year":"2009","unstructured":"Howie, B. N., Donnelly, P. & Marchini, J. A flexible and accurate genotype imputation method for the next generation of genome-wide association studies. PLoS Genet. 5, e1000529 (2009).","journal-title":"PLoS Genet."},{"key":"1784_CR92","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/nrg2796","volume":"11","author":"J Marchini","year":"2010","unstructured":"Marchini, J. & Howie, B. Genotype imputation for genome-wide association studies. Nat. Rev. Genet. 11, 499\u2013511 (2010).","journal-title":"Nat. Rev. Genet."},{"key":"1784_CR93","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1016\/j.ajhg.2009.09.017","volume":"85","author":"L Huang","year":"2009","unstructured":"Huang, L., Wang, C. & Rosenberg, N. A. The relationship between imputation error and statistical power in genetic association studies in diverse populations. Am. J. Hum. Genet. 85, 692\u2013698 (2009).","journal-title":"Am. J. Hum. Genet."},{"key":"1784_CR94","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1007\/s10654-017-0321-4","volume":"32","author":"MA Ikram","year":"2017","unstructured":"Ikram, M. A. et al. The Rotterdam Study: 2018 update on objectives, design and main results. Eur. J. Epidemiol. 32, 807\u2013850 (2017).","journal-title":"Eur. J. Epidemiol."},{"key":"1784_CR95","doi-asserted-by":"publisher","first-page":"2464","DOI":"10.1093\/hmg\/ddr120","volume":"20","author":"WD Ramdas","year":"2011","unstructured":"Ramdas, W. D. et al. Common genetic variants associated with open-angle glaucoma. Hum. Mol. Genet. 20, 2464\u20132471 (2011).","journal-title":"Hum. Mol. Genet."},{"key":"1784_CR96","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1038\/s41588-020-0599-0","volume":"52","author":"PG Hysi","year":"2020","unstructured":"Hysi, P. G. et al. Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia. Nat. Genet. 52, 401\u2013407 (2020).","journal-title":"Nat. Genet."},{"key":"1784_CR97","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/bioinformatics\/btq340","volume":"26","author":"CJ Willer","year":"2010","unstructured":"Willer, C. J., Li, Y. & Abecasis, G. R. METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26, 2190\u20132191 (2010).","journal-title":"Bioinformatics"},{"key":"1784_CR98","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-288","volume":"11","author":"R Magi","year":"2010","unstructured":"Magi, R. & Morris, A. P. GWAMA: software for genome-wide association meta-analysis. BMC Bioinform. 11, 288 (2010).","journal-title":"BMC Bioinform."},{"key":"1784_CR99","doi-asserted-by":"crossref","unstructured":"Benjamini, Y. & Hochberg, Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J. R. Statistical Soci. Ser. B (Methodological) 57, 289\u2013300 (1995).","DOI":"10.1111\/j.2517-6161.1995.tb02031.x"},{"key":"1784_CR100","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1038\/ng.3406","volume":"47","author":"B Bulik-Sullivan","year":"2015","unstructured":"Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236\u20131241 (2015).","journal-title":"Nat. Genet."},{"key":"1784_CR101","doi-asserted-by":"publisher","first-page":"1318","DOI":"10.1038\/s41588-018-0193-x","volume":"50","author":"Y Zhang","year":"2018","unstructured":"Zhang, Y., Qi, G., Park, J. H. & Chatterjee, N. Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits. Nat. Genet. 50, 1318\u20131326 (2018).","journal-title":"Nat. Genet."},{"key":"1784_CR102","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1038\/ng.3097","volume":"46","author":"AR Wood","year":"2014","unstructured":"Wood, A. R. et al. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat. Genet. 46, 1173\u20131186 (2014).","journal-title":"Nat. Genet."},{"key":"1784_CR103","doi-asserted-by":"publisher","first-page":"W65","DOI":"10.1093\/nar\/gks364","volume":"40","author":"AZ Dayem Ullah","year":"2012","unstructured":"Dayem Ullah, A. Z., Lemoine, N. R. & Chelala, C. SNPnexus: a web server for functional annotation of novel and publicly known genetic variants (2012 update). Nucleic Acids Res. 40, W65\u2013W70 (2012).","journal-title":"Nucleic Acids Res."},{"key":"1784_CR104","doi-asserted-by":"publisher","first-page":"D896","DOI":"10.1093\/nar\/gkw1133","volume":"45","author":"J MacArthur","year":"2017","unstructured":"MacArthur, J. et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 45, D896\u2013D901 (2017).","journal-title":"Nucleic Acids Res."},{"key":"1784_CR105","doi-asserted-by":"publisher","first-page":"132","DOI":"10.3109\/13816810.2015.1005317","volume":"36","author":"XD Hao","year":"2015","unstructured":"Hao, X. D., Chen, P., Chen, Z. L., Li, S. X. & Wang, Y. Evaluating the association between keratoconus and reported genetic loci in a Han chinese population. Ophthalmic Genet. 36, 132\u2013136 (2015).","journal-title":"Ophthalmic Genet."},{"key":"1784_CR106","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1038\/ng.2756","volume":"45","author":"HJ Westra","year":"2013","unstructured":"Westra, H. J. et al. Systematic identification of trans eQTLs as putative drivers of known disease associations. Nat. Genet. 45, 1238\u20131243 (2013).","journal-title":"Nat. Genet."},{"key":"1784_CR107","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-35871-w","volume":"8","author":"AF McRae","year":"2018","unstructured":"McRae, A. F. et al. Identification of 55,000 Replicated DNA Methylation QTL. Sci. Rep. 8, 17605 (2018).","journal-title":"Sci. Rep."},{"key":"1784_CR108","doi-asserted-by":"crossref","unstructured":"Segre, A. V. et al. Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. PLoS Genet 6, e1001058 (2010).","DOI":"10.1371\/journal.pgen.1001058"},{"key":"1784_CR109","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","volume":"102","author":"A Subramanian","year":"2005","unstructured":"Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545\u201315550 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1784_CR110","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1038\/s41588-019-0351-9","volume":"51","author":"R Ratnapriya","year":"2019","unstructured":"Ratnapriya, R. et al. Retinal transcriptome and eQTL analyses identify genes associated with age-related macular degeneration. Nat. Genet. 51, 606\u2013610 (2019).","journal-title":"Nat. Genet."},{"key":"1784_CR111","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02317-2","volume":"9","author":"Z Zhu","year":"2018","unstructured":"Zhu, Z. et al. Causal associations between risk factors and common diseases inferred from GWAS summary data. Nat. Commun. 9, 224 (2018).","journal-title":"Nat. Commun."},{"key":"1784_CR112","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","volume":"88","author":"J Yang","year":"2011","unstructured":"Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76\u201382 (2011).","journal-title":"Am. J. Hum. Genet."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-01784-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-01784-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-01784-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T14:24:53Z","timestamp":1670077493000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-01784-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,1]]},"references-count":112,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["1784"],"URL":"https:\/\/doi.org\/10.1038\/s42003-021-01784-0","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,1]]},"assertion":[{"value":"6 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 March 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"H.C. is an Editorial Board Member for Communications Biology, but was not involved in the editorial review of, nor the decision to publish, this article. The authors declare the following competing interests: D.O. holds non-commercial research grants with Rayner Inc and Avedro Inc, holds stock in Sparca Inc. All other authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"266"}}