Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population.
Cell Rep
; 42(5): 112510, 2023 05 30.
Article
em En
| MEDLINE
| ID: mdl-37171956
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
/
Proteínas de Ligação a Tacrolimo
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Miopia
Tipo de estudo:
Prognostic_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article