The Molecular Genetics of High Myopia

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DESCRIPTION (provided by applicant): 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.