The rs1800211 SNP showed moderate significant association in our cohort, but we did not replicate significance of the 2 SNPs more highly associated in the Japanese cohort. This warrants further investigation, as the rs1800211 SNP is exonic, and exhibits potential functional implications for the protein.
No results have implicated more than just a single gene, or have expanded into an analysis of a specific pathway. This may implicate additional genes in a pathway also shown to be risk factors for myopia in validation studies and point to potential haplotype-specific treatments. No candidate genes have been shown to account for even a modest fraction of the familial risk of myopia, and for most the data are conflicting about whether a true association exists. The genes underlying all high-grade myopia peaks except for chromosome Xq28 remain unidentified, suggesting substantial genetic heterogeneity. Consideration is needed to assess the role of environmental factors to genetic influences, such as interactions of early-age near-work and genotype.10,164 Consideration also needs to be given to the identification of phenotypes indicating etiologically homogeneous subgroups, e.g., early age-of-onset, with/without retinal degenerative changes, or classification by individual response to treatments that reduce accommodation to near objects, such as progressive addition lens use.165 Candidate gene studies underscore that myopia is very complex, in fact, so complex that single candidate gene studies are unlikely to demonstrate the type of relationships needed to account for the majority of susceptibility genes. There is a need for a genome-wide approach, incorporating candidate genes but not restricted to the study of candidate genes, to explore the relative contributions and interactions between known candidate genes and possibly novel genes in increased myopia susceptibility.
I thank the members of the myopia families for their cooperation in the multiple projects.
This study was supported by grants from National Institute of Health (RO1 EY014685), NIH CIDR contract N01-HG-65,403, and the Research to Prevent Blindness, Inc.
Terri L. Young
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