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Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely <jats:italic>STON2<\/jats:italic> rs2371597 (<jats:italic>P<\/jats:italic>\u2009=\u20092.32 \u00d7 10<jats:sup>\u221213<\/jats:sup>), and confirmed a significant association between <jats:italic>STON2<\/jats:italic> rs2371597 and keratoconus development (<jats:italic>P<\/jats:italic>\u2009=\u20090.041). Additionally, strong <jats:italic>STON2<\/jats:italic> expression was observed in mouse corneal epithelial basal cells. We also identified <jats:italic>SMAD3<\/jats:italic> rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM\u2019s Watson question answering computer system (<jats:italic>P<\/jats:italic>\u2009=\u20090.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development.<\/jats:p>","DOI":"10.1038\/s42003-020-01137-3","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T10:05:51Z","timestamp":1596189951000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson"],"prefix":"10.1038","volume":"3","author":[{"given":"Yoshikatsu","family":"Hosoda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7410-3764","authenticated-orcid":false,"given":"Masahiro","family":"Miyake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Meguro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuharu","family":"Tabara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachiko","family":"Iwai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Ueda-Arakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eri","family":"Nakano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Mori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munemitsu","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideo","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1128-4729","authenticated-orcid":false,"given":"Chiea-Chuen","family":"Khor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seang-Mei","family":"Saw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-885X","authenticated-orcid":false,"given":"Ching-Yu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhisa","family":"Mizuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akitaka","family":"Tsujikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9354-8558","authenticated-orcid":false,"given":"Kenji","family":"Yamashiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Nagahama Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuharu","family":"Tabara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Kawaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Setoh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshimitsu","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeo","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinji","family":"Kosugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,31]]},"reference":[{"key":"1137_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. 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