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

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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).

authors

  • Williams, Constance
  • 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 CW
  • Plomin, Robert
  • Hammond, Christopher J
  • Mackey, David A
  • He, Mingguang
  • Saw, Seang-Mei
  • Williams, Cathy
  • Guggenheim, Jeremy A

publication date

  • May 2016