TY - JOUR
T1 - Childhood gene-environment interactions and age-dependent effects of genetic variants associated with refractive error and myopia
T2 - The CREAM Consortium
AU - Fan, Qiao
AU - Guo, Xiaobo
AU - Tideman, Jan Willem L
AU - Woolf, Katie Williams
AU - Yazar, Seyhan
AU - Hosseini, S Mohsen
AU - Howe, Laura D
AU - St Pourcain, Beate
AU - Evans, David M.
AU - Timpson, Nicholas J.
AU - McMahon, George
AU - Hysi, Pirro G
AU - Krapohl, Eva Maria Laura
AU - Wang, Ya Xing
AU - Jonas, Jost B
AU - Baird, Paul N.
AU - Wang, Jie Jin
AU - Cheng, Yu-Ching
AU - Teo, Yik Ying
AU - Wong, Tien Yin
AU - Ding, Xiaohu
AU - Wojciechowski, Robert
AU - Young, Terri L.
AU - Parssinen, Olavi
AU - Oexle, Konrad
AU - Pfeiffer, Norbert
AU - Wilson, Joan E Bailey
AU - Paterson, Andrew D.
AU - Klaver, Caroline C. W.
AU - Plomin, Robert Joseph
AU - Hammond, Christopher John
AU - Mackey, David A.
AU - He, Mingguang
AU - Saw, Seang-Mei
AU - Williams, Cathy
AU - Guggenheim, Jeremy
AU - The CREAM Consortium
PY - 2016/5/13
Y1 - 2016/5/13
N2 - 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).
AB - 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).
UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291519/
UR - http://www.scopus.com/inward/record.url?scp=84985997831&partnerID=8YFLogxK
U2 - 10.1038/srep25853
DO - 10.1038/srep25853
M3 - Article
SN - 2045-2322
JO - Scientific Reports
JF - Scientific Reports
ER -