| Title: | Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population |
| Journal: | Cell Reports |
| Published: | 11 May 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37171956/ |
| DOI: | https://doi.org/10.1016/j.celrep.2023.112510 |
| URL: | http://www.cell.com/article/S2211124723005211/pdf |
Publication 7835
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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.27 Authors
- Jianzhong Su
- Jian Yuan
- Liangde Xu
- Shilai Xing
- Mengru Sun
- Yinghao Yao
- Yunlong Ma
- Fukun Chen
- Longda Jiang
- Kai Li
- Xiangyi Yu
- Zhengbo Xue
- Yaru Zhang
- Dandan Fan
- Ji Zhang
- Hui Liu
- Xinting Liu
- Guosi Zhang
- Hong Wang
- Meng Zhou
- Fan Lyu
- Gang An
- Xiaoguang Yu
- Myopia Associated Genetics and Intervention Consortium
- Yuanchao Xue
- Jian Yang
- Jia Qu
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