Repeat polymorphisms underlie top genetic risk loci for glaucoma and colorectal cancer.
Cell
; 186(17): 3659-3673.e23, 2023 08 17.
Article
em En
| MEDLINE
| ID: mdl-37527660
ABSTRACT
Many regions in the human genome vary in length among individuals due to variable numbers of tandem repeats (VNTRs). To assess the phenotypic impact of VNTRs genome-wide, we applied a statistical imputation approach to estimate the lengths of 9,561 autosomal VNTR loci in 418,136 unrelated UK Biobank participants and 838 GTEx participants. Association and statistical fine-mapping analyses identified 58 VNTRs that appeared to influence a complex trait in UK Biobank, 18 of which also appeared to modulate expression or splicing of a nearby gene. Non-coding VNTRs at TMCO1 and EIF3H appeared to generate the largest known contributions of common human genetic variation to risk of glaucoma and colorectal cancer, respectively. Each of these two VNTRs associated with a >2-fold range of risk across individuals. These results reveal a substantial and previously unappreciated role of non-coding VNTRs in human health and gene regulation.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Canais de Cálcio
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Neoplasias Colorretais
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Glaucoma
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Repetições Minissatélites
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Fator de Iniciação 3 em Eucariotos
Tipo de estudo:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2023
Tipo de documento:
Article