期刊
SCIENTIFIC REPORTS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/srep25853
关键词
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资金
- Wellcome Trust [102215/2/13/2]
- UK Medical Research Council [MC_UU_12013/3, MC_UU_12013/4, G0901245, G0500079]
- Hong Kong Polytechnic University [Z0GM]
- Australian National Health and Medical Research Council (NHMRC)
- NHMRC Medical Genomics Grant
- National Institutes of Health (NIH)/National Eye Institute (NEI) [RO1EY018246]
- Clifford Craig Medical Research Trust
- Ophthalmic Research Institute of Australia (ORIA)
- American Health Assistance Foundation (AHAF)
- Peggy and Leslie Cranbourne Foundation
- Foundation for Children
- NHMRC [350415]
- Center for Inherited Diseases Research (CIDR)
- National Science Foundation [81125007]
- Fundamental Research Funds for the State Key Laboratory, NSFC [11401600]
- Fundamental Research Funds for the Central Universities [15lgpy07]
- SYSU-CMU Shunde International Joint Research Institute
- University of Western Australia (UWA)
- Telethon Institute for Child Health Research
- Raine Medical Research Foundation
- UWA Faculty of Medicine
- Dentistry and Health Sciences
- Women's and Infant's Research Foundation
- Curtin University
- Australian National Health and Medical Research Council (NHMRC) [1021105]
- LEI
- Australian Foundation for the Prevention of Blindness
- Singapore BioMedical Research Council (BMRC)
- Singapore Tissue Network
- NMRC [1176/2008]
- US National Institutes of Health [HD044454, HD059215]
- Medical Research Council Research Professorship award [G19/2]
- European Research Council Advanced Investigator award [295366]
- Medical Research Council Clinical Research Training Fellowship
- Institute of Psychiatry, Psychology and Neuroscience Excellence Studentship
- National Eye Institute, National Institutes of Health [R01-EY016379]
- Research to Prevent Blindness, New York, NY
- Intramural Research Program of the National Human Genome Research Institute, NIH
- Research to Prevent Blindness, Inc.
- NIH [NEI R01EY014685]
- Jack Brockhoff Foundation
- Pfizer Australia Senior Research Fellowship
- MRC [MC_UU_12013/3, G0500079, G19/2, MC_UU_12015/1, MR/N003284/1, MR/K023721/1, G0901245, MC_UU_12013/4, MC_UU_12013/5] Funding Source: UKRI
- Medical Research Council [G0500079, MC_U106179471, MC_UU_12013/4, MR/N003284/1, MC_PC_13048, G1000143, MC_UU_12013/5, MC_UU_12015/1, G0901245, MR/K023721/1, G19/2, MC_UU_12013/3, G0401527, MC_PC_15018] Funding Source: researchfish
- National Institute for Health Research [SRF/01/010, SRF-2015-08-005, NF-SI-0512-10114] Funding Source: researchfish
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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