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, Mingguang He, Seang Mei Saw, Jeremy A. Guggenheim, Akira Meguro, Alan F. Wright, Alex W. Hewitt, Alvin L. Young, Amutha Barathi Veluchamy, Andres Metspalu, Angela Döring, Anthony P. Khawaja, Barbara E. Klein, Beate St Pourcain, Brian Fleck, Caroline C.W. Klaver, Caroline Hayward, Cathy Williams, Cécile Delcourt, Chi Pui Pang, Chiea Chuen Khor, Christian Gieger, Claire L. Simpson, Cornelia M. Van Duijn, David A. Mackey, Dwight Stambolian, Emily 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

Research output: Journal article publicationJournal articleAcademic researchpeer-review

77 Citations (Scopus)


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
JournalScientific Reports
Publication statusPublished - 13 May 2016
Externally publishedYes

ASJC Scopus subject areas

  • General


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