Cohort profile: design and methods in the eye and vision consortium of UK Biobank

PURPOSE: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. PARTICIPANTS: UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. FINDINGS TO DATE: A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. FUTURE PLANS: UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life

Measures of socioeconomic status and self-reported glaucoma in the UK Biobank cohort

Purpose: To determine ocular, demographic, and socioeconomic associations with self-reported glaucoma in the UK Biobank.Methods: Biobank is a study of UK residents aged 40–69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112?690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined.Results: In all, 1916 (1.7%) people in UK Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs 56.7 years, P<0.001) and male (2.1% vs 1.4%, P=0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, P<0.001) and Asian (2.14%, P=0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18?mm?Hg both eyes, P<0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P<0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P<0.001) compared with those without (16?mm?Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was ?0.72 for those reporting glaucoma and ?0.95 for those without (P<0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (<£18?000/year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (P<0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect.Conclusions: In a large UK cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions

Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development

A genetic contribution to refractive error has been confirmed by the discovery of more than 150 associated variants in genome-wide association studies (GWAS). Environmental factors such as education and time outdoors also demonstrate strong associations. Currently however, the extent of gene-environment or gene-gene interactions in myopia is unknown. We tested the hypothesis that refractive error-associated variants exhibit effect size heterogeneity, a hallmark feature of genetic interactions. Of 146 variants tested, evidence of non-uniform, non-linear effects were observed for 66 (45%) at Bonferroni-corrected significance (P < 1.1 × 10−4) and 128 (88%) at nominal significance (P < 0.05). LAMA2 variant rs12193446, for example, had an effect size varying from −0.20 diopters (95% CI −0.18 to −0.23) to −0.89 diopters (95% CI −0.71 to −1.07) in different individuals. SNP effects were strongest at the phenotype extremes and weaker in emmetropes. A parsimonious explanation for these findings is that gene-environment or gene-gene interactions in myopia are pervasive

Socioeconomic risk factors and age-related macular degeneration in the UK Biobank study

OBJECTIVE: There is contrasting evidence on the relationship between socioeconomic status (SES) and age-related macular degeneration (AMD), the most common cause of visual impairment (VI) in developed countries. This study examines the relationship between SES, cardiovascular risk factors and self-reported AMD. METHODS AND ANALYSIS: Over 500000 people participated in the UK Biobank study from 2006 to 2019, with sociodemographic data and clinical measurements collected using standardised procedures. Visual acuity was measured in 117907 participants with VI defined as LogMAR ≤0.3. We used logistic regression to examine the cross-sectional associations between SES and self-reported AMD. RESULTS: Self-reported AMD was available for 133339 participants aged 50 and older. People reporting AMD had higher academic qualifications, lower income, were unable to work due to disability, have higher BMI, diabetes and vascular heart disease after adjusting for age and sex. In a multivariable analysis, higher income was protective of AMD and economic inactivity due to disability increased the odds of AMD (2.02, 95% CI 1.13 to 3.61). Both associations were independent of cardiovascular factors, but was no longer significant after adjusting for VI. CONCLUSIONS: The association between education, employment and household income with AMD was independent of cardiovascular risk factors

Eye advance online publication

Abstract Purpose To determine ocular, demographic, and socioeconomic associations with selfreported glaucoma in the UK Biobank. Methods Biobank is a study of UK residents aged 40-69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112 690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined. Results In all, 1916 (1.7%) people in UK Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs 56.7 years, Po0.001) and male (2.1% vs 1.4%, P = 0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, Po0.001) and Asian (2.14%, P = 0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18 mm Hg both eyes, Po0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, Po0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, Po0.001) compared with those without (16 mm Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was − 0.72 for those reporting glaucoma and − 0.95 for those without (Po0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (o£18 000/ year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (Po0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect. Conclusions In a large UK cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions

Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries

10.1038/s41467-020-20851-4Nature Communications121125