3.2
Twins Studies and Myopia
Maria Schäche*,† and Paul N. Baird†
Twins provide a unique resource with which to study the influence of genetic and environmental factors on the development of myopia. In this chapter we review some of the methodological approaches that have been used in twin cohorts to quantitate the extent of involvement of genes in myopia and its underlying determinants such as axial length, anterior chamber depth, and corneal curvature. The use of twins to study the association of myopia with other factors such as birth weight, body stature, and personality will also be discussed.
Introduction
Myopia is defined as a complex trait as its underlying causes are both genetic and environmental in origin. Environmental factors such as excessive reading, high educational attainment, and urbanization1–3 have been suggested as risk factors in its etiology, but more recently, studies by Rose et al. (2008) and Dirani et al. (2009) have suggested that increased exposure to outdoor activity may be protective for myopia, but their results remain under debate.3,4 The known environmental factors account for approximately 11.6% of the phenotypic variation seen with myopia, which suggests that there are other, as yet, unidentified factors that also play a major role in its development.
Evidence supporting a genetic origin for myopia has come from several sources including familial correlation studies, association studies, and genetic linkage studies. Data suggests that children of myopic parents are
*Corresponding author. E-mail: mschache@unimelb.edu.au.
†Centre for Eye Research Australia, University of Melbourne, Royal Victoria Eye and Ear Hospital, 32 Gisborne Street, East Melbourne, Victoria 3002, Australia.
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at four times greater risk of developing myopia than children with no myopic parents.5,6 In support of this, genetic linkage studies in large multigenerational families have suggested over 27 loci are involved in the development of myopia.7 In this chapter, the discussion will focus predominately on twin studies and touch very briefly on family studies only for comparative purposes.
A complete understanding of the underlying causes of myopia requires a survey of both the environmental and genetic influences on the condition. This chapter will describe the application of twin studies in measuring the genetic and environmental components of myopia. A description of the most commonly used methodologies will be provided, including the advantages and limitations of each. This chapter is not intended to be a comprehensive review of all the methodological approaches using twins in genetic studies, but will instead focus on those that have been used to study myopia.
This chapter begins with some important definitions and a historical perspective on how the use of twins in genetic studies of myopia originated. Only articles written in English or those with English translations have been reviewed.
Definition of Myopia
Any genetic study into myopia, or other conditions, must begin with a clear definition of the phenotype (physical presentation). The simplest approach is to define myopia as a type of refractive error that affects visual acuity. In the case of myopia, parallel light rays entering the eye are focussed in front of the retina, resulting in blurred distance vision. Myopia is clinically defined using Spherical Equivalent (SE) measures that are quantitated using units of dioptres (D). Typically, individuals having dioptre readings of −0.5 D or less in one or both eyes are considered to be myopic with further classifications into low (–0.5 D to –2.99 D), moderate (–3.00 D to –5.99 D) and high myopia (<–6.0 D). Whilst these categorical definitions are commonly used and accepted, there is some debate as to the validity of using relatively arbitrary clinical cut-offs. An alternative way to define myopia is to broaden the definition and consider the entire spectrum of refraction measures, from hypermetropia (positive refractive values) to emmetropia and myopia (negative refractive values). This approach considers refraction as a quantitative trait that can influence