Meta-analysis of 542,934 subjects of European ancestry identifies new genes and mechanisms predisposing to refractive error and myopia

Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies...

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Vydáno v:Nature genetics Ročník 52; číslo 4; s. 401 - 407
Hlavní autoři: Hysi, Pirro G., Choquet, Hélène, Khawaja, Anthony P., Wojciechowski, Robert, Tedja, Milly S., Yin, Jie, Simcoe, Mark J., Patasova, Karina, Mahroo, Omar A., Thai, Khanh K., Cumberland, Phillippa M., Melles, Ronald B., Verhoeven, Virginie J. M., Vitart, Veronique, Segre, Ayellet, Stone, Richard A., Wareham, Nick, Hewitt, Alex W., Mackey, David A., Klaver, Caroline C. W., MacGregor, Stuart, Khaw, Peng T., Foster, Paul J., Guggenheim, Jeremy A., Rahi, Jugnoo S., Jorgenson, Eric, Hammond, Christopher J.
Médium: Journal Article
Jazyk:angličtina
Vydáno: New York Nature Publishing Group US 01.04.2020
Nature Publishing Group
Témata:
631/208/205
631/208/212
631/208/457
692/699
Adult
Aged
Agriculture
Analysis
Animal Genetics and Genomics
Biobanks
Biomedical and Life Sciences
Biomedicine
Cancer Research
Circadian rhythms
Consortia
Cornea
Errors
Eye
Female
Gene Function
Gene loci
Genes
Genetic analysis
Genetic diversity
Genetic factors
Genetic Predisposition to Disease - genetics
Genetic variance
Genome-wide association studies
Genome-Wide Association Study - methods
Genomes
Genomics
Heritability
Human Genetics
Humans
Male
Meta-analysis
Middle Aged
Molecular modelling
Morbidity
Mutation
Myopia
Myopia - genetics
Pigmentation
Polymorphism, Single Nucleotide - genetics
Refractive errors
Refractive Errors - genetics
White People - genetics
Europe
United Kingdom > UK
ISSN:1061-4036, 1546-1718, 1546-1718
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Popis
Shrnutí:Refractive errors, in particular myopia, are a leading cause of morbidity and disability worldwide. Genetic investigation can improve understanding of the molecular mechanisms that underlie abnormal eye development and impaired vision. We conducted a meta-analysis of genome-wide association studies (GWAS) that involved 542,934 European participants and identified 336 novel genetic loci associated with refractive error. Collectively, all associated genetic variants explain 18.4% of heritability and improve the accuracy of myopia prediction (area under the curve (AUC) = 0.75). Our results suggest that refractive error is genetically heterogeneous, driven by genes that participate in the development of every anatomical component of the eye. In addition, our analyses suggest that genetic factors controlling circadian rhythm and pigmentation are also involved in the development of myopia and refractive error. These results may enable the prediction of refractive error and the development of personalized myopia prevention strategies in the future. Meta-analysis of genome-wide association studies of 542,934 individuals identifies 336 novel loci associated with refractive error and implicates eye development, circadian rhythm and pigmentation pathways in controlling myopia.
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P.G.H., J.S.R., E.J. and C.J.H. conceived and designed the study. P.T.K., P.J.F., J.S.R. contribute to the collection of data. P.G.H., H.C., A.P.K., R.W., M.S.T., J.Y., K.K.T., P.M.C., V.V., J.A.G and E.J. performed statistical analysis. A.P.K., M.J.S., K.P., K.K.T., AS and J.A.G. performed post-GWAS follow-up analyses. P.G.H., H.C., A.P.K., R.W., J.S.R., E.J., C.J.H. wrote the manuscript with help from O.A.M., P.M.C., R.B.M., V.J.M.V., A.S., R.A.S., N.W., A.W.H., D.A.M., C.C.W.K., S.M., P.T.K., P.J.F. and J.A.G. who helped with the interpretation of the results.
These authors jointly led this work
These authors jointly supervised this work
Author Contributions
ISSN:1061-4036
1546-1718
1546-1718
DOI:10.1038/s41588-020-0599-0