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Multi-trait genome-wide association study identifies new loci associated with optic disc parameters
A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881308/ https://www.ncbi.nlm.nih.gov/pubmed/31798171 http://dx.doi.org/10.1038/s42003-019-0634-9 |
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author | Bonnemaijer, Pieter W. M. Leeuwen, Elisabeth M. van Iglesias, Adriana I. Gharahkhani, Puya Vitart, Veronique Khawaja, Anthony P. Simcoe, Mark Höhn, René Cree, Angela J. Igo, Rob P. Gerhold-Ay, Aslihan Nickels, Stefan Wilson, James F. Hayward, Caroline Boutin, Thibaud S. Polašek, Ozren Aung, Tin Khor, Chiea Chuen Amin, Najaf Lotery, Andrew J. Wiggs, Janey L. Cheng, Ching-Yu Hysi, Pirro G. Hammond, Christopher J. Thiadens, Alberta A. H. J. MacGregor, Stuart Klaver, Caroline C. W. Duijn, Cornelia M. van |
author_facet | Bonnemaijer, Pieter W. M. Leeuwen, Elisabeth M. van Iglesias, Adriana I. Gharahkhani, Puya Vitart, Veronique Khawaja, Anthony P. Simcoe, Mark Höhn, René Cree, Angela J. Igo, Rob P. Gerhold-Ay, Aslihan Nickels, Stefan Wilson, James F. Hayward, Caroline Boutin, Thibaud S. Polašek, Ozren Aung, Tin Khor, Chiea Chuen Amin, Najaf Lotery, Andrew J. Wiggs, Janey L. Cheng, Ching-Yu Hysi, Pirro G. Hammond, Christopher J. Thiadens, Alberta A. H. J. MacGregor, Stuart Klaver, Caroline C. W. Duijn, Cornelia M. van |
author_sort | Bonnemaijer, Pieter W. M. |
collection | PubMed |
description | A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH. |
format | Online Article Text |
id | pubmed-6881308 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68813082019-12-03 Multi-trait genome-wide association study identifies new loci associated with optic disc parameters Bonnemaijer, Pieter W. M. Leeuwen, Elisabeth M. van Iglesias, Adriana I. Gharahkhani, Puya Vitart, Veronique Khawaja, Anthony P. Simcoe, Mark Höhn, René Cree, Angela J. Igo, Rob P. Gerhold-Ay, Aslihan Nickels, Stefan Wilson, James F. Hayward, Caroline Boutin, Thibaud S. Polašek, Ozren Aung, Tin Khor, Chiea Chuen Amin, Najaf Lotery, Andrew J. Wiggs, Janey L. Cheng, Ching-Yu Hysi, Pirro G. Hammond, Christopher J. Thiadens, Alberta A. H. J. MacGregor, Stuart Klaver, Caroline C. W. Duijn, Cornelia M. van Commun Biol Article A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH. Nature Publishing Group UK 2019-11-27 /pmc/articles/PMC6881308/ /pubmed/31798171 http://dx.doi.org/10.1038/s42003-019-0634-9 Text en © The Author(s) 2019 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/. |
spellingShingle | Article Bonnemaijer, Pieter W. M. Leeuwen, Elisabeth M. van Iglesias, Adriana I. Gharahkhani, Puya Vitart, Veronique Khawaja, Anthony P. Simcoe, Mark Höhn, René Cree, Angela J. Igo, Rob P. Gerhold-Ay, Aslihan Nickels, Stefan Wilson, James F. Hayward, Caroline Boutin, Thibaud S. Polašek, Ozren Aung, Tin Khor, Chiea Chuen Amin, Najaf Lotery, Andrew J. Wiggs, Janey L. Cheng, Ching-Yu Hysi, Pirro G. Hammond, Christopher J. Thiadens, Alberta A. H. J. MacGregor, Stuart Klaver, Caroline C. W. Duijn, Cornelia M. van Multi-trait genome-wide association study identifies new loci associated with optic disc parameters |
title | Multi-trait genome-wide association study identifies new loci associated with optic disc parameters |
title_full | Multi-trait genome-wide association study identifies new loci associated with optic disc parameters |
title_fullStr | Multi-trait genome-wide association study identifies new loci associated with optic disc parameters |
title_full_unstemmed | Multi-trait genome-wide association study identifies new loci associated with optic disc parameters |
title_short | Multi-trait genome-wide association study identifies new loci associated with optic disc parameters |
title_sort | multi-trait genome-wide association study identifies new loci associated with optic disc parameters |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881308/ https://www.ncbi.nlm.nih.gov/pubmed/31798171 http://dx.doi.org/10.1038/s42003-019-0634-9 |
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