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Rare variant analyses across multiethnic cohorts identify novel genes for refractive error

Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have b...

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Autores principales: Musolf, Anthony M., Haarman, Annechien E. G., Luben, Robert N., Ong, Jue-Sheng, Patasova, Karina, Trapero, Rolando Hernandez, Marsh, Joseph, Jain, Ishika, Jain, Riya, Wang, Paul Zhiping, Lewis, Deyana D., Tedja, Milly S., Iglesias, Adriana I., Li, Hengtong, Cowan, Cameron S., Biino, Ginevra, Klein, Alison P., Duggal, Priya, Mackey, David A., Hayward, Caroline, Haller, Toomas, Metspalu, Andres, Wedenoja, Juho, Pärssinen, Olavi, Cheng, Ching-Yu, Saw, Seang-Mei, Stambolian, Dwight, Hysi, Pirro G., Khawaja, Anthony P., Vitart, Veronique, Hammond, Christopher J., van Duijn, Cornelia M., Verhoeven, Virginie J. M., Klaver, Caroline C. W., Bailey-Wilson, Joan E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9810640/
https://www.ncbi.nlm.nih.gov/pubmed/36596879
http://dx.doi.org/10.1038/s42003-022-04323-7
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author Musolf, Anthony M.
Haarman, Annechien E. G.
Luben, Robert N.
Ong, Jue-Sheng
Patasova, Karina
Trapero, Rolando Hernandez
Marsh, Joseph
Jain, Ishika
Jain, Riya
Wang, Paul Zhiping
Lewis, Deyana D.
Tedja, Milly S.
Iglesias, Adriana I.
Li, Hengtong
Cowan, Cameron S.
Biino, Ginevra
Klein, Alison P.
Duggal, Priya
Mackey, David A.
Hayward, Caroline
Haller, Toomas
Metspalu, Andres
Wedenoja, Juho
Pärssinen, Olavi
Cheng, Ching-Yu
Saw, Seang-Mei
Stambolian, Dwight
Hysi, Pirro G.
Khawaja, Anthony P.
Vitart, Veronique
Hammond, Christopher J.
van Duijn, Cornelia M.
Verhoeven, Virginie J. M.
Klaver, Caroline C. W.
Bailey-Wilson, Joan E.
author_facet Musolf, Anthony M.
Haarman, Annechien E. G.
Luben, Robert N.
Ong, Jue-Sheng
Patasova, Karina
Trapero, Rolando Hernandez
Marsh, Joseph
Jain, Ishika
Jain, Riya
Wang, Paul Zhiping
Lewis, Deyana D.
Tedja, Milly S.
Iglesias, Adriana I.
Li, Hengtong
Cowan, Cameron S.
Biino, Ginevra
Klein, Alison P.
Duggal, Priya
Mackey, David A.
Hayward, Caroline
Haller, Toomas
Metspalu, Andres
Wedenoja, Juho
Pärssinen, Olavi
Cheng, Ching-Yu
Saw, Seang-Mei
Stambolian, Dwight
Hysi, Pirro G.
Khawaja, Anthony P.
Vitart, Veronique
Hammond, Christopher J.
van Duijn, Cornelia M.
Verhoeven, Virginie J. M.
Klaver, Caroline C. W.
Bailey-Wilson, Joan E.
author_sort Musolf, Anthony M.
collection PubMed
description Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions.
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spelling pubmed-98106402023-01-05 Rare variant analyses across multiethnic cohorts identify novel genes for refractive error Musolf, Anthony M. Haarman, Annechien E. G. Luben, Robert N. Ong, Jue-Sheng Patasova, Karina Trapero, Rolando Hernandez Marsh, Joseph Jain, Ishika Jain, Riya Wang, Paul Zhiping Lewis, Deyana D. Tedja, Milly S. Iglesias, Adriana I. Li, Hengtong Cowan, Cameron S. Biino, Ginevra Klein, Alison P. Duggal, Priya Mackey, David A. Hayward, Caroline Haller, Toomas Metspalu, Andres Wedenoja, Juho Pärssinen, Olavi Cheng, Ching-Yu Saw, Seang-Mei Stambolian, Dwight Hysi, Pirro G. Khawaja, Anthony P. Vitart, Veronique Hammond, Christopher J. van Duijn, Cornelia M. Verhoeven, Virginie J. M. Klaver, Caroline C. W. Bailey-Wilson, Joan E. Commun Biol Article Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions. Nature Publishing Group UK 2023-01-03 /pmc/articles/PMC9810640/ /pubmed/36596879 http://dx.doi.org/10.1038/s42003-022-04323-7 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Musolf, Anthony M.
Haarman, Annechien E. G.
Luben, Robert N.
Ong, Jue-Sheng
Patasova, Karina
Trapero, Rolando Hernandez
Marsh, Joseph
Jain, Ishika
Jain, Riya
Wang, Paul Zhiping
Lewis, Deyana D.
Tedja, Milly S.
Iglesias, Adriana I.
Li, Hengtong
Cowan, Cameron S.
Biino, Ginevra
Klein, Alison P.
Duggal, Priya
Mackey, David A.
Hayward, Caroline
Haller, Toomas
Metspalu, Andres
Wedenoja, Juho
Pärssinen, Olavi
Cheng, Ching-Yu
Saw, Seang-Mei
Stambolian, Dwight
Hysi, Pirro G.
Khawaja, Anthony P.
Vitart, Veronique
Hammond, Christopher J.
van Duijn, Cornelia M.
Verhoeven, Virginie J. M.
Klaver, Caroline C. W.
Bailey-Wilson, Joan E.
Rare variant analyses across multiethnic cohorts identify novel genes for refractive error
title Rare variant analyses across multiethnic cohorts identify novel genes for refractive error
title_full Rare variant analyses across multiethnic cohorts identify novel genes for refractive error
title_fullStr Rare variant analyses across multiethnic cohorts identify novel genes for refractive error
title_full_unstemmed Rare variant analyses across multiethnic cohorts identify novel genes for refractive error
title_short Rare variant analyses across multiethnic cohorts identify novel genes for refractive error
title_sort rare variant analyses across multiethnic cohorts identify novel genes for refractive error
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9810640/
https://www.ncbi.nlm.nih.gov/pubmed/36596879
http://dx.doi.org/10.1038/s42003-022-04323-7
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