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

Qiao Fan, Xiaobo Guo, J. Willem L. Tideman, Katie M. Williams, Seyhan Yazar, S. Mohsen Hosseini, Laura D. Howe, Beaté St Pourcain, David M. Evans, Nicholas J. Timpson, George McMahon, Pirro G. Hysi, Eva Krapohl, Ya Xing Wang, Jost B. Jonas, Paul Nigel Baird, Jie Jin Wang, Ching Yu Cheng, Yik Ying Teo, Tien Yin WongXiaohu Ding, Robert Wojciechowski, Terri L. Young, Olavi Pärssinen, Konrad Oexle, Norbert Pfeiffer, Joan E. Bailey-Wilson, Andrew D. Paterson, Caroline C.W. Klaver, Robert Plomin, Christopher J. Hammond, David A. Mackey, Mingguang He, Seang Mei Saw, Cathy Williams, Jeremy A. Guggenheim, The CREAM Consortium , Alex W. Hewitt, Jamie E. Craig, Jing Hua Zhao, Kathryn P. Burdon, Paul J. Foster, Rhys D. Fogarty

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    Abstract

    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).

    Original languageEnglish
    Article number25853
    Number of pages14
    JournalScientific Reports
    Volume6
    DOIs
    Publication statusPublished - 13 May 2016

    Keywords

    • CREAM Consortium
    • Myopia
    • refractive error
    • age-dependent effects
    • Childhood gene-environment interactions

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