Understanding how genetic and environmental risk factors combine to cause short-sightedness

Why was the research important?

In recent decades, short-sightedness (myopia) has become increasingly common throughout the world. About half of the UK population is now short-sighted. As well as the inconvenience of needing to wear glasses or contact lenses, people who are severely short-sighted have a higher risk of developing eye conditions that cause permanent sight loss.

Recent studies indicate that myopic macular degeneration is already one of the 3 leading causes of blindness globally. By 2050 some 5 billion people – half the world’s population – will be short-sighted, compared to around 1.4 billion today.

Once patients become short-sighted, their condition can be controlled, but not cured. Therefore prevention is widely viewed as the best approach to reducing the number of people suffering sight-loss as a result of myopia.

While studies of twins have shown that myopia is a highly hereditable condition, the doubling of its prevalence in Europe over the course of 1-2 generations means that it cannot be explained by genetics alone. Large-scale population studies have already identified several environmental risk factors associated with myopia. The current consensus is that both genetics and lifestyle factors influence who becomes short-sighted and to what degree, but a greater understanding of how these factors interact is needed if the condition is to be prevented.

What was the aim of the project?

The goal of this project was to identify genetic differences that made some people more likely to become short-sighted than others, when exposed to the same environmental risk factors.

In order to complete their analyses, the team used data from 2 existing cohorts: UK Biobank, and the Avon Longitudinal Study of Parents and Children (ALSPAC). UK Biobank is the world’s largest biomedical database and health research resource, containing in-depth genetic and health information on over 500,000 UK participants. It also contains questionnaire data on the age at which data subjects started to wear glasses or contact lenses for myopia, and has information from ophthalmic assessments on a sub-set of approximately 107,000 participants.

ALSPAC followed the progression of eye conditions in some 9,000 children. Both study cohorts contain detailed lifestyle information over the course of childhood, which enabled the interaction between genes and environmental risk factors to be studied in depth.

As recent research had already demonstrated that short-sightedness is more common in people who go into further or higher education, Professor Guggenheim’s team set up analyses to identify genetic variants that differed in effect, depending on the number of years spent in full-time education.

They also set up analyses to test for “variance heterogeneity”: a hallmark of genetic variants that are involved either in gene-environment, or gene-gene interactions.

What was the outcome?

Analyses designed to discover genes whose contribution to short-sightedness depended solely on a person’s level of education identified very few such genes. Furthermore, the gene variants that were found have very modest effects on the risk of myopia.

To provide a more general strategy for finding genes whose risk profile for short-sightedness depended on wider lifestyle factors, rather than education specifically, the team examined the full complement of 150 gene variants, known from worldwide collaborative genetic studies to be associated with the risk of short-sightedness, for evidence of genetic variance heterogeneity.

The results of this work showed that most of the gene variants that influence susceptibility to short-sightedness have effects that are heightened by undergoing more years of schooling or exposure to other lifestyle-related risk factors.

A further observation from this research project was the remarkably high level of variability between participants. All prior studies of this topic had made the assumption that risk factors for myopia produce the same effect in everybody, but Professor Guggenheim’s research revealed that this was not the case. His team found that genetic and lifestyle risk factors were found to vary in their impact on short-sightedness by a factor of more than 6-fold.

The important implication of this new finding was that a person’s genetic predisposition for myopia is not the whole story. Rather, the degree of short-sightedness that an individual child will develop seems to depend on their exposure to other lifestyle, or other genetic risk factors.

How will this research help to beat sight loss faster?

Current treatments that are used to control myopia, such as low-dose atropine drops, have been shown to slow its progression by 40-50%, but there is consensus amongst the research community that preventing the condition in the first place will be key to stopping a global health problem.

The findings from this project are very encouraging because they indicate that modifying a child’s environment - for example, their school environment - might be a successful approach to preventing myopia, whatever the child’s level of genetic predisposition.

Further information

Sight Research UK is currently funding a project, led by Dr Denize Atan at the University of Bristol, which is examining the effect of insulin in the body on myopia, and how that relationship is further influenced by environmental and genetic factors. We are also supporting Dr Veronique Vitart, at the University of Edinburgh, who is researching the genetic risk factors associated with retinal detachment arising from severe myopia.

Not everyone who is severely short-sighted will develop other eye conditions, and for most people, their eyes will be healthy. The best way for everyone to look after their eyes is to have regular eye tests. An optician can spot early signs of eye conditions before you experience any symptoms, many of which can be treated if detected early enough. You can read about what’s involved in having an eye test here.

You can find more about the causes and symptoms of myopia and pathological myopia here.