Myopia, or nearsightedness, is the most common human eye disorder in the world, and is a significant global public health concern. Along with cataract, macular degeneration, infectious disease, and vitamin A deficiency, myopia is one of the most important causes of visual impairment worldwide. Severe or high-grade myopia is a leading cause of blindness because of its associated ocular morbidities of retinal detachment, macular choroidal degeneration, premature cataract, and glaucoma. Ample evidence documents the heritability of the non-syndromic forms of this condition, especially for high-grade myopia, commonly referred to as myopic spherical refractive power of 5-6 diopters or higher. Multiple high-grade myopia genetic loci have been identified in studies primarily performed in our laboratories. Confirmatory and additional studies identifying myopia loci have also occurred in other research laboratories. In general, myopia susceptibility genes are unknown with few association studies performed, and without confirmation in other research laboratories or testing of separate patient cohorts. Our international consortium is composed of myopia and statistical geneticists from the United Kingdom, France, Denmark, Australia, and the United States. Over the course of the past 8 years we have ascertained and obtained DNA samples on more than 250 family units primarily of Northern European descent with high- grade myopia. Within this international cohort, we have established significant heritability and/or familial aggregation for myopia. All of our samples for DNA are in hand and have been verified for genotyping. We gained approval for a single nucleotide polymorphism (SNP) genome screen at the Center for Inherited Disease Research (CIDR) of the National Institutes of Health to identify loci associated with the high-grade myopia condition. Mapping and association analyses are in process for the genotyping data provided by CIDR. Detailed plans for follow-up studies for established linkage intervals have been devised which include replication studies.

Public Health Relevance

Our international myopia consortium represents one of the largest assemblies of families and cases with high-grade, sight-threatening myopia at an early age, carefully collected to document clinical phenotypes and related covariates. This unique and precious resource will be the basis for the proposed study of the genetic influences for exaggerated eye growth leading to myopic development. We hypothesize that the identification of myopia susceptibility genes will not only provide insight into the molecular basis of this significant eye disorder, but will also identify pathways involved in eye growth and development. This effort may lead to effective therapies to treat or potentially prevent this common eye condition.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
Project #
Application #
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Wiggs, Cheri
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Duke University
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Kuo, Anthony N; Verkicharla, Pavan K; McNabb, Ryan P et al. (2016) Posterior Eye Shape Measurement With Retinal OCT Compared to MRI. Invest Ophthalmol Vis Sci 57:OCT196-203
Souma, Tomokazu; Tompson, Stuart W; Thomson, Benjamin R et al. (2016) Angiopoietin receptor TEK mutations underlie primary congenital glaucoma with variable expressivity. J Clin Invest 126:2575-87
Tkatchenko, Andrei V; Luo, Xiaoyan; Tkatchenko, Tatiana V et al. (2016) Large-Scale microRNA Expression Profiling Identifies Putative Retinal miRNA-mRNA Signaling Pathways Underlying Form-Deprivation Myopia in Mice. PLoS One 11:e0162541
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
McKnight, Charlotte M; Sherwin, Justin C; Yazar, Seyhan et al. (2014) Myopia in young adults is inversely related to an objective marker of ocular sun exposure: the Western Australian Raine cohort study. Am J Ophthalmol 158:1079-85
Lim, Sing-Hui; St Germain, Elizabeth; Tran-Viet, Khanh-Nhat et al. (2014) Sequencing analysis of the ATOH7 gene in individuals with optic nerve hypoplasia. Ophthalmic Genet 35:1-6
Springelkamp, Henriët; Höhn, René; Mishra, Aniket et al. (2014) Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun 5:4883
McClements, Michelle; Davies, Wayne I L; Michaelides, Michel et al. (2013) Variations in opsin coding sequences cause x-linked cone dysfunction syndrome with myopia and dichromacy. Invest Ophthalmol Vis Sci 54:1361-9
Lim, Sing-Hui; Tran-Viet, Khanh-Nhat; Yanovitch, Tammy L et al. (2013) CYP1B1, MYOC, and LTBP2 mutations in primary congenital glaucoma patients in the United States. Am J Ophthalmol 155:508-517.e5
Tran-Viet, Khanh-Nhat; Soler, Vincent; Quiette, Valencia et al. (2013) Mutation in collagen II alpha 1 isoforms delineates Stickler and Wagner syndrome phenotypes. Mol Vis 19:759-66

Showing the most recent 10 out of 58 publications