47 Gene-Environment Interactions in the Aetiology of Myopia

Demonstrating gene-environment interactions in the etiology of myopia and other refractive errors, requires analysis of three specific questions:

•Do genetic differences contribute to phenotypic variations in myopia?

•Do environmental exposures contribute to phenotypic variations in myopia?

•Is there evidence of differential sensitivity of the different genotypes characterized to environmental changes?

Aetiological Heterogeneity of Myopia

Analysis of these questions is complicated by the fact that myopia is clearly heterogeneous in etiology, with relatively rare, clearly genetic severe forms, and a broad category of school-juvenile-onset or “acquired” myopia, which is generally mild to moderate in severity. This has become by far the most common form in many populations.5

Clearly genetic forms of myopia

Myopia is a common feature of a number of syndromes, such as Marfan and Stickler syndromes. These are commonly, but not exclusively, associated with mutations that affect connective tissue, and are typically early onset and severe, with clear familial patterns of inheritance. There are also several forms of early onset, severe, familial myopia, where the primary characteristic is excessive axial elongation and myopia, often referred to as the non-syndromic high myopias. The linked characteristics of early onset and severity make these forms of myopia important from a clinical perspective, because of their association with chorioretinal pathologies.

Many of these forms of myopia clearly have a major genetic component, and indeed, a number of relevant genes and chromosomal localizations have been identified (for reviews see Refs. 6 and 7). These forms of myopia may be relatively resistant to environmental variations. Candidate gene analysis has supported a role for polymorphisms in collagen isoforms, particularly COL2A1,8 hepatocyte growth factor9 and transforming growth factor beta1.10 However, in total, these forms of myopia account for only few percent of myopia in the population.