Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium
Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loc...
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| Format: | Online |
| Language: | English |
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865831/ |
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pubmed-48658312016-05-23 Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium Fan, Qiao Guo, Xiaobo Tideman, J. Willem L. Williams, Katie M. Yazar, Seyhan Hosseini, S. Mohsen Howe, Laura D. Pourcain, Beaté St Evans, David M. Timpson, Nicholas J. McMahon, George Hysi, Pirro G. Krapohl, Eva Wang, Ya Xing Jonas, Jost B. Baird, Paul Nigel Wang, Jie Jin Cheng, Ching-Yu Teo, Yik-Ying Wong, Tien-Yin Ding, Xiaohu Wojciechowski, Robert Young, Terri L. Pärssinen, Olavi Oexle, Konrad Pfeiffer, Norbert Bailey-Wilson, Joan E. Paterson, Andrew D. Klaver, Caroline C. W. Plomin, Robert Hammond, Christopher J. Mackey, David A. He, Mingguang Saw, Seang-Mei Williams, Cathy Guggenheim, Jeremy A. Article Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable visual impairment. Genome-wide association studies (GWAS) in adults have identified 39 loci associated with refractive error and myopia. Here, the age-of-onset of association between genetic variants at these 39 loci and refractive error was investigated in 5200 children assessed longitudinally across ages 7–15 years, along with gene-environment interactions involving the major environmental risk-factors, nearwork and time outdoors. Specific variants could be categorized as showing evidence of: (a) early-onset effects remaining stable through childhood, (b) early-onset effects that progressed further with increasing age, or (c) onset later in childhood (N = 10, 5 and 11 variants, respectively). A genetic risk score (GRS) for all 39 variants explained 0.6% (P = 6.6E–08) and 2.3% (P = 6.9E–21) of the variance in refractive error at ages 7 and 15, respectively, supporting increased effects from these genetic variants at older ages. Replication in multi-ancestry samples (combined N = 5599) yielded evidence of childhood onset for 6 of 12 variants present in both Asians and Europeans. There was no indication that variant or GRS effects altered depending on time outdoors, however 5 variants showed nominal evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4; P = 6.3E–04). Nature Publishing Group 2016-05-13 /pmc/articles/PMC4865831/ /pubmed/27174397 http://dx.doi.org/10.1038/srep25853 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Fan, Qiao Guo, Xiaobo Tideman, J. Willem L. Williams, Katie M. Yazar, Seyhan Hosseini, S. Mohsen Howe, Laura D. Pourcain, Beaté St Evans, David M. Timpson, Nicholas J. McMahon, George Hysi, Pirro G. Krapohl, Eva Wang, Ya Xing Jonas, Jost B. Baird, Paul Nigel Wang, Jie Jin Cheng, Ching-Yu Teo, Yik-Ying Wong, Tien-Yin Ding, Xiaohu Wojciechowski, Robert Young, Terri L. Pärssinen, Olavi Oexle, Konrad Pfeiffer, Norbert Bailey-Wilson, Joan E. Paterson, Andrew D. Klaver, Caroline C. W. Plomin, Robert Hammond, Christopher J. Mackey, David A. He, Mingguang Saw, Seang-Mei Williams, Cathy Guggenheim, Jeremy A. |
| spellingShingle |
Fan, Qiao Guo, Xiaobo Tideman, J. Willem L. Williams, Katie M. Yazar, Seyhan Hosseini, S. Mohsen Howe, Laura D. Pourcain, Beaté St Evans, David M. Timpson, Nicholas J. McMahon, George Hysi, Pirro G. Krapohl, Eva Wang, Ya Xing Jonas, Jost B. Baird, Paul Nigel Wang, Jie Jin Cheng, Ching-Yu Teo, Yik-Ying Wong, Tien-Yin Ding, Xiaohu Wojciechowski, Robert Young, Terri L. Pärssinen, Olavi Oexle, Konrad Pfeiffer, Norbert Bailey-Wilson, Joan E. Paterson, Andrew D. Klaver, Caroline C. W. Plomin, Robert Hammond, Christopher J. Mackey, David A. He, Mingguang Saw, Seang-Mei Williams, Cathy Guggenheim, Jeremy A. Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium |
| author_facet |
Fan, Qiao Guo, Xiaobo Tideman, J. Willem L. Williams, Katie M. Yazar, Seyhan Hosseini, S. Mohsen Howe, Laura D. Pourcain, Beaté St Evans, David M. Timpson, Nicholas J. McMahon, George Hysi, Pirro G. Krapohl, Eva Wang, Ya Xing Jonas, Jost B. Baird, Paul Nigel Wang, Jie Jin Cheng, Ching-Yu Teo, Yik-Ying Wong, Tien-Yin Ding, Xiaohu Wojciechowski, Robert Young, Terri L. Pärssinen, Olavi Oexle, Konrad Pfeiffer, Norbert Bailey-Wilson, Joan E. Paterson, Andrew D. Klaver, Caroline C. W. Plomin, Robert Hammond, Christopher J. Mackey, David A. He, Mingguang Saw, Seang-Mei Williams, Cathy Guggenheim, Jeremy A. |
| author_sort |
Fan, Qiao |
| title |
Childhood gene-environment interactions and age-dependent effects of genetic variants
associated with refractive error and myopia: The CREAM Consortium |
| title_short |
Childhood gene-environment interactions and age-dependent effects of genetic variants
associated with refractive error and myopia: The CREAM Consortium |
| title_full |
Childhood gene-environment interactions and age-dependent effects of genetic variants
associated with refractive error and myopia: The CREAM Consortium |
| title_fullStr |
Childhood gene-environment interactions and age-dependent effects of genetic variants
associated with refractive error and myopia: The CREAM Consortium |
| title_full_unstemmed |
Childhood gene-environment interactions and age-dependent effects of genetic variants
associated with refractive error and myopia: The CREAM Consortium |
| title_sort |
childhood gene-environment interactions and age-dependent effects of genetic variants
associated with refractive error and myopia: the cream consortium |
| description |
Myopia, currently at epidemic levels in East Asia, is a leading cause of untreatable
visual impairment. Genome-wide association studies (GWAS) in adults have identified
39 loci associated with refractive error and myopia. Here, the age-of-onset of
association between genetic variants at these 39 loci and refractive error was
investigated in 5200 children assessed longitudinally across ages 7–15
years, along with gene-environment interactions involving the major environmental
risk-factors, nearwork and time outdoors. Specific variants could be categorized as
showing evidence of: (a) early-onset effects remaining stable through childhood, (b)
early-onset effects that progressed further with increasing age, or (c) onset later
in childhood (N = 10, 5 and 11 variants, respectively). A
genetic risk score (GRS) for all 39 variants explained 0.6%
(P = 6.6E–08) and 2.3%
(P = 6.9E–21) of the variance in refractive
error at ages 7 and 15, respectively, supporting increased effects from these
genetic variants at older ages. Replication in multi-ancestry samples (combined
N = 5599) yielded evidence of childhood onset for 6 of 12
variants present in both Asians and Europeans. There was no indication that variant
or GRS effects altered depending on time outdoors, however 5 variants showed nominal
evidence of interactions with nearwork (top variant, rs7829127 in ZMAT4;
P = 6.3E–04). |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4865831/ |
| _version_ |
1613578925187792896 |