학술논문
Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5promoter predisposing to high myopia in a Han Chinese population
Document Type
Article
Author
Su, Jianzhong; Yuan, Jian; Xu, Liangde; Xing, Shilai; Sun, Mengru; Yao, Yinghao; Ma, Yunlong; Chen, Fukun; Jiang, Longda; Li, Kai; Yu, Xiangyi; Xue, Zhengbo; Zhang, Yaru; Fan, Dandan; Zhang, Ji; Liu, Hui; Liu, Xinting; Zhang, Guosi; Wang, Hong; Zhou, Meng; Lyu, Fan; An, Gang; Yu, Xiaoguang; Xue, Yuanchao; Yang, Jian; Qu, Jia
Source
Cell Reports; May 2023, Vol. 42 Issue: 5
Subject
Language
ISSN
22111247
Abstract
High myopia (HM) is one of the leading causes of visual impairment and blindness worldwide. Here, we report a whole-exome sequencing (WES) study in 9,613 HM cases and 9,606 controls of Han Chinese ancestry to pinpoint HM-associated risk variants. Single-variant association analysis identified three newly identified -genetic loci associated with HM, including an East Asian ancestry-specific low-frequency variant (rs533280354) in FKBP5. Multi-ancestry meta-analysis with WES data of 2,696 HM cases and 7,186 controls of European ancestry from the UK Biobank discerned a newly identified European ancestry-specific rare variant in FOLH1. Functional experiments revealed a mechanism whereby a single G-to-A transition at rs533280354 disrupted the binding of transcription activator KLF15 to the promoter of FKBP5, resulting in decreased transcription of FKBP5. Furthermore, burden tests showed a significant excess of rare protein-truncating variants among HM cases involved in retinal blood vessel morphogenesis and neurotransmitter transport.