Keratoconus-susceptibility gene identification by corneal thickness genome-wide association study and artificial intelligence IBM Watson
Yoshikatsu Hosoda, Masahiro Miyake, Akira Meguro, Yasuharu Tabara, Sachiko Iwai, Naoko Ueda‐Arakawa, Eri Nakano, Yuki Mori, Munemitsu Yoshikawa, Hideo Nakanishi, Chiea Chuen Khor, Seang‐Mei Saw, Ryo Yamada, Fumihiko Matsuda, Ching‐Yu Cheng, Nobuhisa Mizuki, Akitaka Tsujikawa, Kenji Yamashiro, The Nagahama Study Group, Yasuharu Tabara, Takahisa Kawaguchi, Kazuya Setoh, Fumihiko Matsuda, Yoshimitsu Takahashi, Takeo Nakayama, Shinji Kosugi
Abstract
Abstract Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. 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 STON2 rs2371597 ( P = 2.32 × 10 −13 ), and confirmed a significant association between STON2 rs2371597 and keratoconus development ( P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM’s Watson question answering computer system ( P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development.