Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population
Summary: 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 identifi...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723005211 |
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| author | 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 Yuanchao Xue Jian Yang Jia Qu |
| author_facet | 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 Yuanchao Xue Jian Yang Jia Qu |
| author_sort | Jianzhong Su |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-09T13:14:48Z |
| format | Article |
| id | doaj.art-966fa0251c6f46bcbc996825c60ed414 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T13:14:48Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-966fa0251c6f46bcbc996825c60ed4142023-05-12T04:16:20ZengElsevierCell Reports2211-12472023-05-01425112510Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese populationJianzhong Su0Jian Yuan1Liangde Xu2Shilai Xing3Mengru Sun4Yinghao Yao5Yunlong Ma6Fukun Chen7Longda Jiang8Kai Li9Xiangyi Yu10Zhengbo Xue11Yaru Zhang12Dandan Fan13Ji Zhang14Hui Liu15Xinting Liu16Guosi Zhang17Hong Wang18Meng Zhou19Fan Lyu20Gang An21Xiaoguang Yu22Yuanchao Xue23Jian Yang24Jia Qu25School of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou 325101, Zhejiang, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325011, China; Corresponding authorSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaNational Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Institute of PSI Genomics, Wenzhou 325024, ChinaKey Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100190, ChinaOujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou 325101, Zhejiang, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325011, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, ChinaWenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325011, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou 325101, Zhejiang, ChinaInstitute of PSI Genomics, Wenzhou 325024, ChinaInstitute of PSI Genomics, Wenzhou 325024, ChinaSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100190, China; Corresponding authorSchool of Life Sciences, Westlake University, Hangzhou, Zhejiang 310030, China; Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang 310024, China; Corresponding authorSchool of Ophthalmology & Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou 325027, China; Oujiang Laboratory, Zhejiang Lab for Regenerative Medicine, Vision and Brain Health, Wenzhou 325101, Zhejiang, China; Wenzhou Institute, University of Chinese Academy of Sciences, Wenzhou 325011, China; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723005211CP: Genomics |
| spellingShingle | 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 Yuanchao Xue Jian Yang Jia Qu Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population Cell Reports CP: Genomics |
| title | Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population |
| title_full | Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population |
| title_fullStr | Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population |
| title_full_unstemmed | Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population |
| title_short | Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population |
| title_sort | sequencing of 19 219 exomes identifies a low frequency variant in fkbp5 promoter predisposing to high myopia in a han chinese population |
| topic | CP: Genomics |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723005211 |
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