An investigation of the genetic basis of myopia in the 1958 British birth cohort

Lead Research Organisation: University College London
Department Name: Unlisted


Myopia (short-sightedness) affects at least one in five of the population in the UK and similar countries. All affected individuals have difficulty seeing distant objects, impacting on a range of activities such as driving, sports and going to the cinema or theatre, and some are also unable to focus on near objects, unless they are held at very close range. Affected people are at considerably increased risk of retinal detachment and retinal scarring, both of which can cause blindness. Myopia is recognised to have an important impact on the lives of affected individuals and incurs high social and economic costs, for example the costs of optical treatment (glasses and/or contact lenses) in the USA alone in 1990 were estimated to be US $5 billion. There is good evidence that it is becoming more common in many populations. Despite long being an area of active scientific research, there has been little study of how genetic and other biological, environmental, socio-economic and life-style factors, from birth to adult life, combine to influence its occurrence or progression.
We propose to investigate the role of recently reported possible genetic factors in causing myopia in the members of the 1958 British birth cohort. This comprises all 17,000 people born in one week in 1958, who have been followed at intervals since that time by interview or examination. This genetic project will draw on, and run in parallel with, an epidemiological project already underway examining myopia both as an outcome and as a risk factor, combining information on general health, development and lifestyle. If we can confirm and refine these genetic factors in the 1958 cohort, this will improve our understanding of the genetic contribution to myopia and inform future work exploring the relationship between genetic and developmental, life-style and social factors in the development of myopia. In the longer term, we would hope that this knowledge would ultimately contribute to developing new methods of preventing or treating myopia, including those targeted at environmental risk factors in those predisposed genetically as well as gene therapy itself.

Technical Summary

Abstract of research:
Myopia affects at least one in five people in the UK and similar countries and the WHO has identified the prevention and treatment of myopia as a global priority, in recognition of its impact on the lives of affected individuals as well as its attendant high social and economic costs. The recent marked and unexplained increase in the prevalence and severity of myopia in many parts of the world identifies the pressing need for new large-scale scientifically integrated programmes of population-based research in which both the genetic and environmental influences on the onset, severity and progression of this complex disorder are examined. This work will inform the development of prevention and treatment strategies in the longer term.
The broad aim of this proposal is to establish a programme of genetic epidemiological work on myopia by building on our existing life-course epidemiological investigation of myopia and other ophthalmic disorders in the 1958 British birth cohort and by capitalising on the new opportunity for molecular genetics work provided by the first collection of DNA on cohort members. This work will further understanding of the genetic influences on the development of refractive error and elucidation of gene-environment interactions in the aetiology of myopia. Specifically, we will apply quantitative trait loci analytical methods to investigate 1200 cohort members comprising the outer tertiles of refractive error (as measured by autorefraction in a random 2000 subsample of the entire cohort) in order to:
- identify genes with a high likelihood of influencing the development of myopia in this nationally representative population, using candidates, chosen on the basis of their likely biological function together with their location in areas of interest (11p13, 3q26, 8p23, 4q12), generated from a recent large UK sib-pair study.
- identify specific nucleotide sequences within such genes that show the strongest association with refractive error and which might act directly at the molecular level to influence emmetropisation.
This work is both timely and unique in bringing together substantial research resources and expertise in epidemiology for ophthalmology and child health, with ophthalmic molecular genetics and genetic epidemiology / statistical genetics.


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Description Wellcome Trust Project Grant (A genomewide association study of refractive error in the 1958 British Birth Cohort.)
Amount £591,024 (GBP)
Funding ID 083478 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2008 
End 01/2009
Title Statistical approaches to analysing refractive errror data 
Description We have applied statistical approaches to find optimal ways of analysing refractive error data which have a highly skewed and leptokurtotic distribution, together with considering optimal approaches to transformation of data for the purposes of analysis as a categorical versus continuous trait. This has informed our present Wellcome Trust funded genomewide study of refractive error, which builds directly on the work undertaken in our MRC funded work reported here. 
Type Of Material Data analysis technique 
Year Produced 2009 
Provided To Others? Yes  
Impact We are presently writing up this methodological work as a paper, antinipated submission early 2010 
Description International Consortium on Myopia 
Organisation Guy's and St Thomas' NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Replication and joint analysis
Collaborator Contribution Replication / Joint analysis of genomewide association study.
Impact 1. Paper (Nature Genetics 2010, Hysi et al, as reported earlier) 2. Involvement in an international consortium which is presently taking forward a metanalysis of findings from several genomewide association studies of myopia.
Start Year 2009
Description Primarily 'clinical' meetings, with scientific press and patient groups attending - eg Royal College of Ophthalmologists annual congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Making oral and poster presentations and giving interviews to scientific press

Most notable impact was scientific interest in our work and invitations to collaborate on other programmes of related research.
Year(s) Of Engagement Activity 2007,2008,2009