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Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium

Article scientifique 2016 Anglais

Résumé

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).

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Fan, Q., Guo, X., Tideman, J., Williams, K., Yazar, S., Hosseini, S., Howe, L., Pourcain, B., Timpson, N., McMahon, G., Hysi, P., Krapohl, E., Wang, Y., Baird, P., Teo, Y., Wong, T., Ding, X., Wojciechowski, R., Young, T., Pärssinen, O., Pfeiffer, N., Bailey‐Wilson, J., Paterson, A., Plomin, R., Hammond, C., Mackey, D., He, M., Saw, S., Williams, C., Guggenheim, J., Meguro, A., Wright, A., Hewitt, A., Young, A., Metspalu, A., Döring, A., Khawaja, A., Klein, B., Fleck, B., Hayward, C., Delcourt, C., Pang, C., Khor, C., Gieger, C., Simpson, C., Duijn, C., Stambolian, D., Chew, E., Tai, E., Mihailov, E., Smith, G., Biino, G., Campbell, H., Rudan, I., Seppälä, I., Kaprio, J., Wilson, J., Craig, J., Ried, J., Korobelnik, J., Fondran, J., Liao, J., Zhao, W., Xie, J., Kemp, J., Lass, J., Rahi, J., Wedenoja, J., Mäkelä, K., Burdon, K., Khaw, K., Yamashiro, K., Chen, L., Xu, L., Farrer, L. (2016). Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia: The CREAM Consortium. https://doi.org/10.1038/srep25853

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Auteur(s)

Qiao Fan Xiaobo Guo J. Willem L. Tideman Katie Williams Seyhan Yazar S. Mohsen Hosseini Laura D Howe Beaté St Pourcain Nicholas J. Timpson George McMahon Pirro G. Hysi Eva Krapohl Ya Xing Wang Paul N. Baird Yik-Ying Teo Tien Yin Wong Xiaohu Ding Robert Wojciechowski Terri L. Young Olavi Pärssinen Norbert Pfeiffer Joan E. Bailey‐Wilson Andrew D. Paterson Robert Plomin Christopher J. Hammond David A. Mackey Mingguang He Seang‐Mei Saw Cathy Williams Jeremy A. Guggenheim Akira Meguro Alan F. Wright Alex W. Hewitt Alvin L. Young Andres Metspalu Angela Döring Anthony P. Khawaja Barbara E.K. Klein Brian W. Fleck Caroline Hayward Cécile Delcourt Chi Pui Pang Chiea Chuen Khor Christian Gieger Claire L. Simpson Cornelia M. van Duijn Dwight Stambolian Emily Y. Chew E Shyong Tai Evelin Mihailov George Davey Smith Ginevra Biino Harry Campbell Igor Rudan Ilkka Seppälä Jaakko Kaprio James F. Wilson Jamie E. Craig Janina S. Ried Jean‐François Korobelnik Jeremy Fondran Jiemin Liao Wei Zhao Jing Xie John P. Kemp Jonathan H. Lass Jugnoo S. Rahi Juho Wedenoja Kari-Matti Mäkelä Kathryn P. Burdon Kay‐Tee Khaw Kenji Yamashiro Li Jia Chen Liang Xu Lindsay A. Farrer

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