Refractive errors (myopia and hyperopia) are the most widespread human eye disorders. By the year 2020, one third of the world's population-over 2.5 billion people-will be affected by myopia alone. The global economic productivity loss from uncorrected refractive errors has been estimated to be $268 billion. Hence, refractive errors are a significant Public Health problem, especially in regions of East Asia where myopia has reached ?epidemic? proportions. Refractive errors are complex traits, in which both inherited genetic and environmental/behavioral factors are thought to play significant roles. The objective of this project is to study the effects of gene-environment interactions on ocular refraction within the context of whole-genome association studies. The proposed research will make use of 6 large datasets from genomic studies conducted in the United States, Germany, and Singapore.
Our specific aims are to: 1) discover of genetic polymorphisms which interact with environmental factors in gene-environment-wide interaction studies of refractive error;and 2) identify biological pathways or gene-sets through which environmental factors mediate refractive error development in humans. The ultimate goals of the research are to better understand the complex biology of ocular refractive development, and identify specific genes which interact with environmental factors (as measured by proxies of exposure to high visual demand, such as education and reading) in refractive error. The proposed research is part of a K08 Mentored Clinical Scientist Research Career Development Award. Training in the grant period will focus on developing skills necessary in the design, management, analysis and interpretation of large-scale gene-environment-wide studies. Dr. Wojciechowski's long-term career will be devoted to translating the vast data provided by large genomic studies into clinically useful, comprehensible, and practical information. This information will ultimately benefit scientists, clinicians, Public Health practitioners, policy makers and, most importantly, the public at large.

Public Health Relevance

Refractive errors (myopia and hyperopia) are the most common causes of correctable visual impairment worldwide, and are known to be affected by both the visual environment and inherited genetic factors. This project aims to study the effects of gene-environment interactions on refractive errors on a genome wide level. This research will offer a benefit to the public health by: providing a better understanding of the complex biology of refractive errors;explaining the large differences in the prevalence of myopia among populations;and identifying potential targets amenable to intervention.

National Institute of Health (NIH)
National Eye Institute (NEI)
Clinical Investigator Award (CIA) (K08)
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Special Emphasis Panel (ZEY1-VSN (06))
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Agarwal, Neeraj
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Johns Hopkins University
Public Health & Prev Medicine
Schools of Public Health
United States
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Cuellar-Partida, Gabriel; Lu, Yi; Kho, Pik Fang et al. (2016) Assessing the Genetic Predisposition of Education on Myopia: A Mendelian Randomization Study. Genet Epidemiol 40:66-72
Tkatchenko, Andrei V; Tkatchenko, Tatiana V; Guggenheim, Jeremy A et al. (2015) APLP2 Regulates Refractive Error and Myopia Development in Mice and Humans. PLoS Genet 11:e1005432
Li, Qing; Wojciechowski, Robert; Simpson, Claire L et al. (2015) Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium. Hum Genet 134:131-46
Fan, Qiao; Wojciechowski, Robert; Kamran Ikram, M et al. (2014) Education influences the association between genetic variants and refractive error: a meta-analysis of five Singapore studies. Hum Mol Genet 23:546-54
Hysi, Pirro G; Mahroo, Omar A; Cumberland, Phillippa et al. (2014) Common mechanisms underlying refractive error identified in functional analysis of gene lists from genome-wide association study results in 2 European British cohorts. JAMA Ophthalmol 132:50-6
Hysi, Pirro G; Wojciechowski, Robert; Rahi, Jugnoo S et al. (2014) Genome-wide association studies of refractive error and myopia, lessons learned, and implications for the future. Invest Ophthalmol Vis Sci 55:3344-51
Simpson, Claire L; Wojciechowski, Robert; Oexle, Konrad et al. (2014) Genome-wide meta-analysis of myopia and hyperopia provides evidence for replication of 11 loci. PLoS One 9:e107110
Hysi, Pirro G; Cheng, Ching-Yu; Springelkamp, Henriët et al. (2014) Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma. Nat Genet 46:1126-30
Wojciechowski, Robert; Hysi, Pirro G (2013) Focusing in on the complex genetics of myopia. PLoS Genet 9:e1003442
Simpson, Claire L; Wojciechowski, Robert; Yee, Stephanie S et al. (2013) Regional replication of association with refractive error on 15q14 and 15q25 in the Age-Related Eye Disease Study cohort. Mol Vis 19:2173-86

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