B3675 - Myopia in Young Adults - 15/12/2020

B number: 
Principal applicant name: 
Jeremy A. Guggenheim | School of Optometry & Vision Sciences Cardiff University (United Kingdom)
Dr Cathy Williams, Professor Ian Flitcroft, Professor Stan Zammit, Professor Russ Jago, Professor Peter Blair, Dr Anna Pease
Title of project: 
Myopia in Young Adults
Proposal summary: 

Myopia (short-sightedness) is an eye condition in which distance vision is blurry. People with myopia need to wear glasses or contact lenses, or have laser refractive surgery, to achieve sharp distance vision. When people with myopia get older, they are at a higher-than-average risk of developing permanent sight problems such as macular disease. Myopia typically develops during school age. The reason it develops is not understood, however both genes and lifestyle factors are known to play a role. Children whose parents have myopia inherit a genetic predisposition to develop myopia themselves. In clinical studies, children who are randomly assigned to spend extra time outdoors each day have a lower incidence of myopia, suggesting that spending too little time outdoors is a risk factor. Individuals who spend more years at school also tend to develop a higher level of myopia. Around the world, the prevalence rate of myopia varies widely. This is thought to be related to the variation in the ‘intensity’ of school work and the pressure to do well at school. Myopia has also been linked to mental health problems such as depression and to levels of physical activity. However, for most of these links, it is unclear if myopia is a cause or a consequence of the association.

The ALSPAC cohort is unique in the scale and breadth of the information that has been collected about vision problems in childhood. This includes information about myopia development. In previous studies of ALSPAC participants, our research group has documented the time-course of myopia development and exposure to risk factors or protective factors such as time spent outdoors. For example, children from the ALSPAC cohort who spent relatively less time outdoors than their peers at age 7-years-old were found to have an increased risk of developing myopia by the age of 15. Here, we propose to build on our previous findings. Our primary aim is to discover if myopia is the cause or consequence of its associations with other lifestyle factors and health or wellbeing characteristics. To do this, we will use a technique called Mendelian randomisation, which uses random inheritance of subtle genetic features in a way similar to randomisation of participants in a clinical trial. Usually, Mendelian randomisation studies require very large cohorts of participants – larger than the ALSPAC cohort. However, myopia and many of the related conditions we plan to investigate are highly heritable, which means there is a good prospect of successfully answering our research questions using data collected in a sample the size of the ALSPAC cohort. Our secondary aims are extensions of the primary aim. We will compare the eye characteristics and lifestyle of children growing up in the UK with those of children elsewhere, to investigate if the risks for myopia are similar or different in countries with high or low prevalence rates of myopia. We will also extend our previous studies into the genetics of myopia. The exceptionally high level of detail that the ALSPAC research team has collected about genetics will allow us to test the role of specific genes in conferring a predisposition to myopia, and how this varies depending on the lifestyle risk factors that children are exposed to.

Impact of research: 
As regards lifestyle risk factors, we will seek to confirm previous observational associations and, where possible, use Mendelian randomisation to assess the direction of causality. The findings may aid the design of future randomised controlled trials for interventions designed to reduce myopia progression. As regards genetic risk, our studies may help identify novel genes that confer a risk of myopia. This knowledge may aid the development of drugs capable of slowing myopia progression.
Date proposal received: 
Thursday, 10 December, 2020
Date proposal approved: 
Tuesday, 15 December, 2020
Ophthalmology, Gene mapping, GWAS, Microarrays, RNA, Statistical methods, Genetic epidemiology, Genetics, Genomics, Genome wide association study, Growth, Mendelian randomisation, Physical - activity, fitness, function, Sleep, Vision