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Twins and Myopia — Other Studies
Studies using twins have proved invaluable in determining that genes play a role in the development of myopia, but they have also indicated that environmental factors also play a role, albeit to a lesser extent. There have been many studies assessing the role of environmental factors in the development of myopia, as has been described in detail in Chapter 1.3. Here, we will focus on the handful of studies that have been performed in twins. In particular, the role of body stature, birth weight, educational attainment, and personality will be discussed.
The possibility that intrauterine factors may influence the development of myopia has been explored in a number of studies. A study by Grijbovski et al. (2005) assessed the role of birth weight in the development of multiple traits, including myopia.32 Using a cohort of 2880 monozygotic twins and 4960 dizygotic twins recruited from Norway, Grijbovski et al. (2005) were able to show that birth weight is negatively associated with myopia. In other words, a lower birth weight increases the risk of developing myopia. This opened up the possibility that intrauterine factors that influence birth weight may also impact of the development of myopia later in life. However, this finding was not replicated in a more recent study by Dirani et al. (2009), which suggested there was no statistically significant association between birth weight and myopia.33 Clearly, the potential role of intrauterine factors in myopia remains unclear.
Work has also focussed on physical attributes in adult twins that may influence myopia. This has been undertaken in studies that have tried to define a particular body type (height, weight, body mass index) that may predispose a person to myopia. A study by Teikari et al. (1987) using both twins and singletons suggested that height and body mass index, but not weight, are positively associated with myopia, and that this association is only evident in males.34 In contrast to this, a recent study by Dirani et al. (2009) suggested that height and body mass index are not associated with myopia, but that increased weight is a risk factor for myopia in females.35 The conflicting evidence from these studies suggests that there is unlikely to be a “myopia body type.”
In addition to these attempts to find a “myopia body type,” many studies have also attempted to define behavioral characteristics that may predispose a person to the development of myopia. It has long been believed that myopic individuals have a tendency to certain personality traits such as introversion and conscientiousness. However, an important study by
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van de Berg et al. (2008) suggested that this was certainly not the case, with no association found between myopia and these personality traits. What van de Berg et al. (2008) did find was that myopia was associated with a group of traits referred to as “openness.” “Openness” refers to a group of interrelated personality traits, including the desire to try new things, a tendency towards a vivid imagination, the readiness to re-examine traditional values, and the tendency to be intellectually curious. These results suggested that perhaps there may be an association between education levels and myopia. This association has been confirmed in studies by Lyhne et al. (2001) and Dirani et al. (2008), showing that myopia is associated with increased levels of education.17,36 Furthermore, it has been suggested that educational attainment is also a highly heritable trait (heritability measure of 0.66) and that there is a commonality between the genes related to educational attainment and myopia.36 Thus, both environmental as well as genetic components need to be considered when undertaking studies involving traits such as myopia.
The Importance of Twin Registries
While our focus in this chapter is exclusively on twins and myopia it should be made clear to the reader that twins can be used to study a myriad of traits limited only by the individual investigator’s research interests. To facilitate scientific studies using twins, a number of twin registries have been established around the world. These registries are a national or sometimes regional register of twins and their families that are willing to participate in scientific studies. A number of such twin registries have been used for the study of myopia, including the Australian Twin Registry (ATR), the Danish Twin Registry (DTR), and the St. Thomas’ UK Adult Twin Registry. These registries have been invaluable in being able to recruit twins for such studies as outlined in this chapter. We will now briefly describe these registries and the myopia studies that they have facilitated.
The most utilized twin registry for the study of myopia is by far the ATR. The ATR was established in the 1970’s and is a registry of twins living in Australia.37 The ATR is volunteer based and there is no selection bias in terms of zygosities, ages, or medical history. In essence, any twins born and residing in Australian who are willing to participate in scientific studies are included in the ATR. In total there are over 31,000 twin pairs registered with the ATR, of which 38% are monozygotic, 58% are dizygotic, and
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4% are of unknown zygosities. The ATR has facilitated many major myopia studies including the Genes in Myopia (GEM) Study, which recruited twins from the state of Victoria and the Twins Eye Study in Tasmania, which recruited twins from the state of Tasmania.25,38 A third study, the Brisbane Adolescent Twin Study, also used the ATR as a recruitment source in addition to independent recruitment regionally in the state of Queensland.39
Other twin registries that have proven invaluable in the study of myopia have been the Danish Twin Registry and the St Thomas’ UK Adult Twin Registry.40,41 The Danish Twin Registry is the oldest twin registry in the world, having been established in 1954, and contains at least 75,000 twin pairs. The St Thomas’ UK Adult Twin Registry was established in 1993 and contains at least 10,000 twin pairs. Both these registries have been valuable sources for recruitment of twins for many myopia studies, including heritability studies from Lyhne et al. (2001), Hammond et al. (2001), and Lopes et al. (2009), which we have previously described.16–18
Concluding Comments
In this chapter we have summarized the current methodological approaches that have been used to study twins and myopia. This is by no means a comprehensive description of all experimental designs incorporating twins in the study of heritable traits, but it is a focussed discussion on the methods used with respect to myopia. It is clear that twins can provide a valuable insight into the relative contributions of genes and environment to the development of myopia and its underlying determinants. Despite the methodological limitations, particularly with regards to the classical twin model, current twin studies indicate that myopia is likely to be a highly heritable trait as are its underlying determinants such as axial length.
The next step in the use of twins to understand the etiology of myopia will be to undertake more detailed genetic studies to pinpoint the exact nature of the hereditary factors influencing myopia. This can now be achieved through the use of gene chip technology, which allows up to one million single nucleotide polymorphisms (SNPs) across the entire genome to be assessed in a single association study. Such studies, termed genome-wide association studies (GWAS), can be used to identify gene variants that are associated with myopia. GWAS analysis is statistically
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demanding and findings will require verification in order to confirm their role in myopia (see Chapter 3.4). Furthermore, gene-environment interaction studies will also be required to understand how identified genetic variants interact with environmental factors. However, these issues are beyond the scope of this chapter, but will be covered in Chapter 1.2.
The current chapter has highlighted the power and utility of twins in the study of myopia and indicated that myopia is a complex trait with a polygenic etiology. Twins have therefore provided an extremely useful resource with which we have been able to gain valuable information regarding myopia and it is envisaged that their continued use will allow us to uncover many more facets of myopia in the future.
Acknowledgments
The author’s research on myopia is supported by the Australian Federal Government through a National Health and Medical Research Project Grant (#529912), as well by the Angior Family Foundation.
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