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Design and Methods in the Eye and Vision Consortium of UK Biobank

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Design and Methods in the Eye and Vision Consortium of UK Biobank Open access Cohort profile BMJ Open: first published as 10.1136/bmjopen-2018-025077 on 21 February 2019. Downloaded from Cohort profile: design and methods in the eye and vision consortium of UK Biobank Sharon Yu Lin Chua,1 Dhanes Thomas,1 Naomi Allen,2 Andrew Lotery,3 Parul Desai,1 Praveen Patel,1 Zaynah Muthy,1 Cathie Sudlow,4 Tunde Peto,5 Peng Tee Khaw,1 Paul J Foster,1 UK Biobank Eye & Vision Consortium To cite: Chua SYL, Thomas D, ABSTRACT Strengths and limitations of this study Allen N, et al. Cohort profile: Purpose To describe the rationale, methods and research design and methods in the potential of eye and vision measures available in UK ► UK Biobank is the largest prospective cohort with eye and vision consortium Biobank. of UK Biobank. BMJ Open extensive measures on ophthalmic diseases and Participants UK Biobank is a large, multisite, prospective 2019;9:e025077. doi:10.1136/ conditions. cohort study. Extensive lifestyle and health questionnaires, bmjopen-2018-025077 ► Repeated physical measures every few years and a range of physical measures and collection of biological linkage to National Health Service records will pro- ► Prepublication history for specimens are collected. The scope of UK Biobank was vide valuable information on health outcomes. this paper is available online. extended midway through data collection to include ► A large number of incident cases of eye diseases in To view these files, please visit assessments of other measures of health, including eyes the journal online (http:// dx. doi. 5 years will allow the detection and quantification of and vision. The eye assessment at baseline included org/ 10. 1136/ bmjopen- 2018- small effect sizes. questionnaires detailing past ophthalmic and family 025077). ► A low response rate (5.5%). history, measurement of visual acuity, refractive error Received 3 July 2018 and keratometry, intraocular pressure (IOP), corneal Revised 1 October 2018 biomechanics, spectral domain optical coherence Accepted 11 December 2018 tomography (OCT) of the macula and a disc–macula age-related eye diseases, such as age-related fundus photograph. Since recruitment, UK Biobank has macular degeneration (AMD), diabetic reti- collected accelerometer data and begun multimodal nopathy (DR) and glaucoma, are leading imaging data (including brain, heart and abdominal MRI) causes of visual impairment in Western popu- in 100 000 participants. Dense genotypic data and a panel lations. Increased intraocular pressure (IOP) http://bmjopen.bmj.com/ © Author(s) (or their of 20 biochemistry measures are available, and linkage to is one of the most significant risk factors for medical health records for the full cohort has begun. employer(s)) 2019. Re-use the development4 and progression5 of glau- permitted under CC BY-NC. No Findings to date A total of 502 665 people aged between commercial re-use. See rights 40 and 69 were recruited to participate in UK Biobank. coma. A recent study from the UK Biobank and permissions. Published by Of these, 117 175 took part in baseline assessment of demonstrated that factors including diabetes, BMJ. vision, IOP, refraction and keratometry. A subgroup of height, smoking and black ethnicity have 1 NIHR Biomedical Research 67 321 underwent OCT and retinal photography. The different associations with Goldmann-cor- Centre, Moorfields Eye Hospital introduction of eye and vision measures in UK Biobank related IOP (IOPg) and corneal-compen- NHS Foundation Trust and UCL 6 was accompanied by intensive training, support and a data on September 24, 2021 by guest. Protected copyright. Institute of Ophthalmology, sated IOP (IOPcc). Hence, suggesting that London, UK monitoring quality control process. these factors are related to corneal biome- 2Nuffield Department of Future plans UK Biobank is one of the largest prospective chanical properties. In another UK Biobank Population Health, University of cohorts worldwide with extensive data on ophthalmic study, 67 321 participants underwent optical Oxford, Oxford, UK diseases and conditions. Data collection is an ongoing coherence tomography (OCT) imaging 3Department of Clinical and process and a repeat of the baseline assessment including of both eyes.7 The OCT is a non-invasive Experimental Sciences, the questionnaires, measurements and sample collection University of Southampton, will be performed in subsets of 25 000 participants every imaging system that provides high-resolution, Southampton, UK cross-sectional images of the retina, retinal 4 2–3 years. The depth and breadth of this dataset, coupled Centre for Clinical Brain with its open-access policy, will create a powerful resource nerve fibre layer (RNFL) and the optic nerve, Sciences, University of for all researchers to investigate the eye diseases in later aiding in the diagnosis and management of Edinburgh, Edinburgh, UK 8 5Institute of Clinical Science, life. eye diseases. Loss of vision due to eye diseases Queen’s University Belfast has a considerable impact on an individual’s 9 10 Faculty of Medicine Health and activities and quality of life. Identifying Life Sciences, Belfast, Belfast, INTRODUCTIon modifiable risk factors of common disabling UK Ageing populations worldwide face an diseases of later life may help develop preven- Correspondence to increasing burden of chronic and neurode- tive strategies. These conditions are often 1 Dr Paul J Foster; generative diseases, resulting in substantial caused by a combination of genetics, envi- p. foster@ ucl. ac. uk health and economic burdens.2 3 Chronic ronmental and lifestyle factors. Built on a Chua SYL, et al. BMJ Open 2019;9:e025077. doi:10.1136/bmjopen-2018-025077 1 Open access BMJ Open: first published as 10.1136/bmjopen-2018-025077 on 21 February 2019. Downloaded from foundation laid by the Human Genome Project,11 the COHORT DESCRIPTION last decade has seen dramatic advances in the under- Whole UK Biobank cohort standing of molecular mechanisms in the human health UK Biobank is a large, multisite, study of 502 656 UK and disease. A myriad of studies using traditional linkage residents aged between 40 and 69 years who were regis- methods and genome-wide association studies12–14 have tered with the National Health Service (NHS). The now raised questions about the role of gene–gene (GxG) overall study protocol (http://www. ukbiobank. ac. uk/ and gene–environment (GxE) interaction in deter- resources/) and protocols for individual tests (http:// mining disease susceptibility.15 16 Extensive information biobank. ctsu. ox. ac. uk/ crystal/ catalogs. cgi) are available on environment and lifestyle in conjunction with biolog- online. Briefly, extensive baseline questionnaires and ical samples are crucial to assess GxE interactions. physical measures were obtained from 22 assessment To avoid the potential for reverse causality and minimise centres between January 2006 and October 2010.20 21 This recall bias, exposures should be measured before they are included data on sociodemographics, family history and affected by disease or its treatment. Prospective cohorts early life exposures, psychosocial, environmental, life- offer many advantages for assessing the combined effects style, environmental and health status, hearing threshold of genes, environment and lifestyle factors and its associa- and cognitive function as well as self-reported medical tion with various health outcomes. The prospective nature conditions. In addition to the baseline questionnaire, of these cohorts allows the exposures to be recorded web-based questionnaires were included to obtain data before the disease onset, and a wide range of diseases to on dietary intake, occupational history, cognitive func- be investigated, including those that may be challenging tion, mental health and gastrointestinal symptoms. In to study retrospectively.17 Furthermore, the overall bene- addition, mailed triaxial accelerometers will supplement ficial and adverse effects of a specific exposure on the life- the physical activity data in 100 000 participants.20 time risks of numerous diseases can be examined. Only a Physical examination included blood pressure, heart small proportion of individuals will develop the disease rate, hand grip strength, anthropometrics, spirom- and the effects of various exposures on disease develop- etry, bone density, arterial stiffness, fitness test. Biolog- ment are likely to be modest. Hence, to address questions ical samples, including stored blood, urine and saliva of GxG and GxE interaction, prospective studies need samples, were collected to allow many different types of to include a large number of participants, with several assay (eg, genetic, proteomic, metabolomics, biochemical hundred thousand participants.18 19 However, there is a and haematologic), (https://www. ukbiobank. ac. uk/)22 23 lack of large prospective studies at such a scale that allow providing a uniquely rich resource for investigating aeti- investigation of risk factors or gene–environmental inter- ological risk factors and thereby assisting in the preven- action of eye diseases. tion and treatment of many different conditions. The UK UK Biobank (https://www. ukbiobank. ac. uk/) is a Biobank Axiom array was used for genotyping and the 23 large-scale multisite cohort study, conceived to provide a methods have been described in detail. Furthermore, http://bmjopen.bmj.com/ resource for the scientific community to examine genetic UK Biobank launched the world’s largest health imaging and environmental risk factors for complex diseases of study in 2014
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