Social determinants of ethnic disparities in SARS-CoV-2 infection: UK Biobank SARS-CoV-2 Serology Study.

BACKGROUND: The social determinants of ethnic disparities in risk of SARS-CoV-2 infection during the first wave of the pandemic in the UK remain unclear. METHODS: In May 2020, a total of 20 195 adults were recruited from the general population into the UK Biobank SARS-CoV-2 Serology Study. Between mid-May and mid-November 2020, participants provided monthly blood samples. At the end of the study, participants completed a questionnaire on social factors during different periods of the pandemic. Logistic regression yielded ORs for the association between ethnicity and SARS-CoV-2 immunoglobulin G antibodies (indicating prior infection) using blood samples collected in July 2020, immediately after the first wave. RESULTS: After exclusions, 14 571 participants (mean age 56; 58% women) returned a blood sample in July, of whom 997 (7%) had SARS-CoV-2 antibodies. Seropositivity was strongly related to ethnicity: compared with those of White ethnicity, ORs (adjusted for age and sex) for Black, South Asian, Chinese, Mixed and Other ethnic groups were 2.66 (95% CI 1.94-3.60), 1.66 (1.15-2.34), 0.99 (0.42-1.99), 1.42 (1.03-1.91) and 1.79 (1.27-2.47), respectively. Additional adjustment for social factors reduced the overall likelihood ratio statistics for ethnicity by two-thirds (67%; mostly from occupational factors and UK region of residence); more precise measurement of social factors may have further reduced the association. CONCLUSIONS: This study identifies social factors that are likely to account for much of the ethnic disparities in SARS-CoV-2 infection during the first wave in the UK, and highlights the particular relevance of occupation and residential region in the pathway between ethnicity and SARS-CoV-2 infection.

Cohort profile: rationale and methods of UK Biobank repeat imaging study eye measures to study dementia.

PURPOSE: The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study. PARTICIPANTS: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs. FINDINGS TO DATE: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes. FUTURE PLANS: The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia.

UK Biobank: a globally important resource for cancer research.

UK Biobank is a large-scale prospective study with deep phenotyping and genomic data. Its open-access policy allows researchers worldwide, from academia or industry, to perform health research in the public interest. Between 2006 and 2010, the study recruited 502,000 adults aged 40-69 years from the general population of the United Kingdom. At enrolment, participants provided information on a wide range of factors, physical measurements were taken, and biological samples (blood, urine and saliva) were collected for long-term storage. Participants have now been followed up for over a decade with more than 52,000 incident cancer cases recorded. The study continues to be enhanced with repeat assessments, web-based questionnaires, multi-modal imaging, and conversion of the stored biological samples to genomic and other '-omic' data. The study has already demonstrated its value in enabling research into the determinants of cancer, and future planned enhancements will make the resource even more valuable to cancer researchers. Over 26,000 researchers worldwide are currently using the data, performing a wide range of cancer research. UK Biobank is uniquely placed to transform our understanding of the causes of cancer development and progression, and drive improvements in cancer treatment and prevention over the coming decades.

Identification of host-pathogen-disease relationships using a scalable multiplex serology platform in UK Biobank.

Certain infectious agents are recognised causes of cancer and other chronic diseases. To understand the pathological mechanisms underlying such relationships, here we design a Multiplex Serology platform to measure quantitative antibody responses against 45 antigens from 20 infectious agents including human herpes, hepatitis, polyoma, papilloma, and retroviruses, as well as Chlamydia trachomatis, Helicobacter pylori and Toxoplasma gondii, then assayed a random subset of 9695 UK Biobank participants. We find seroprevalence estimates consistent with those expected from prior literature and confirm multiple associations of antibody responses with sociodemographic characteristics (e.g., lifetime sexual partners with C. trachomatis), HLA genetic variants (rs6927022 with Epstein-Barr virus (EBV) EBNA1 antibodies) and disease outcomes (human papillomavirus-16 seropositivity with cervical intraepithelial neoplasia, and EBV responses with multiple sclerosis). Our accessible dataset is one of the largest incorporating diverse infectious agents in a prospective UK cohort offering opportunities to improve our understanding of host-pathogen-disease relationships with significant clinical and public health implications.

The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions.

UK Biobank is a population-based cohort of half a million participants aged 40-69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world's largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future directions.

Approaches to minimising the epidemiological impact of sources of systematic and random variation that may affect biochemistry assay data in UK Biobank.

Background: UK Biobank is a large prospective study that recruited 500,000 participants aged 40 to 69 years, between 2006-2010.The study has collected (and continues to collect) extensive phenotypic and genomic data about its participants. In order to enhance further the value of the UK Biobank resource, a wide range of biochemistry markers were measured in all participants with an available biological sample. Here, we describe the approaches UK Biobank has taken to minimise error related to sample collection, processing, retrieval and assay measurement. Methods: During routine quality control checks, the laboratory team observed that some assay results were lower than expected for samples acquired during certain time periods. Analyses were undertaken to identify and correct for the unexpected dilution identified during sample processing, and for expected error caused by laboratory drift of assay results. Results: The vast majority (92%) of biochemistry serum assay results were assessed to be not materially affected by dilution, with an estimated difference in concentration of less than 1% (i.e. either lower or higher) than that expected if the sample were unaffected; 8.3% were estimated to be diluted by up to 10%; very few samples appeared to be diluted more than this. Biomarkers measured in urine (creatinine, microalbumin, sodium, potassium) and red blood cells (HbA1c) were not affected. In order to correct for laboratory variation over the assay period, all assay results were adjusted for date of assay, with the exception of those that had a high biological coefficient of variation or evident seasonal variability: vitamin D, lipoprotein (a), gamma glutamyltransferase, C-reactive protein and rheumatoid factor. Conclusions: Rigorous approaches related to sample collection, processing, retrieval, assay measurement and data analysis have been taken to mitigate the impact of both systematic and random variation in epidemiological analyses that use the biochemistry assay data in UK Biobank.

Current and Emerging Solutions to Challenges in the Management of Alzheimer's Disease.

​​​​Effective multifactorial management of Alzheimer's disease (AD) requires a triadic alliance of the clinician, the patient, and the patient's family and/or care partner(s). During the evaluation process and when the diagnosis of AD is delivered, these parties must work together to set goals and develop care plans. Care plans should be designed to help the patient maintain safety and autonomy as long as he or she can and, once autonomy is no longer possible, to allow the patient and care partner(s) to experience as much comfort and the best possible quality of life for as long as possible. In this Academic Highlights, faculty members from neurology, psychiatry, neuropsychology, and primary care share their recommendations, supported by current evidence and guidelines, for handling the complexities of providing care for patients with AD.

A Multidisciplinary Approach for Addressing Challenges in Alzheimer's Disease.

In this webcast, experts from the Banner health care system discuss the evaluation of cognitive concerns and cognitive impairment, and the diagnosis and management of Alzheimer's disease (AD). Topics of the brief video clips include methods for developing therapeutic rapport with patients and their families, identifying and assessing the patient's and/or the care partner's concern, detecting cognitive impairment, characterizing the patient's cognitive-behavioral syndrome, and investigating and determining the etiology of the cognitive impairment or dementia syndrome. The experts also address strategies for delivering a diagnosis to patients and their care partners, planning treatment regimens, and offering education and support. Task-sharing and collaboration must occur between specialists and primary care clinicians to address the growing number of individuals with AD and related dementias.

Cognitive Assessment of Alzheimer's Disease and Dementias in Clinical Practice: Pragmatics of Brief Instruments and Neuropsychological Evaluation.

Detection of cognitive impairment and dementia (CID) through the use of brief cognitive assessment tools (BCATs) is the first step to establishing an accurate diagnosis and care plan for individuals seen in primary practices. While the cognitive-behavioral syndrome and underlying etiology may not be readily apparent through brief assessment, clinicians can refer patients for a more comprehensive neuropsychological evaluation. A timely diagnosis maximizes the potential for patients to be involved in decision-making and planning for their future, and allows for expedited intervention and harm reduction. This activity provides a practical review of validated and standardized BCATs that can aid in the detection of CID; reviews cognitive and neuropsychological domains and their clinical relevance; and delineates circumstances for referral to neuropsychology and the utility of neuropsychological evaluation to practicing clinicians.

Disclosure of Alzheimer's Disease and Dementia: Patient- and Care Partner-Centric Decision-Making and Communication.

Disclosing the diagnosis of cognitive impairment or dementia due to Alzheimer's disease (AD) and Related Dementias (ADRD) can be one of the most challenging aspects of dementia care for clinicians. However difficult the diagnosis is to give or receive, evidence and evidence-based consensus support that disclosing a timely AD/ADRD diagnosis, accompanied by psychoeducation and care planning, is beneficial to patient-care partner dyads. Diagnosis, provided as early as possible, increases the likelihood for patients to be involved in decision-making and planning for their future and allows care options to be implemented sooner to provide greater clinical and quality-of-life benefits, reduce potential for harm, and mitigate symptoms and decline. Using patient-centered communication and following a structured process, clinicians can provide a successful disclosure of diagnosis as a component of the necessary foundation to implement impactful management and care planning for patients and caregivers going through a life-changing process.

Large Scale Population Assessment of Physical Activity Using Wrist Worn Accelerometers: The UK Biobank Study.

BACKGROUND: Physical activity has not been objectively measured in prospective cohorts with sufficiently large numbers to reliably detect associations with multiple health outcomes. Technological advances now make this possible. We describe the methods used to collect and analyse accelerometer measured physical activity in over 100,000 participants of the UK Biobank study, and report variation by age, sex, day, time of day, and season. METHODS: Participants were approached by email to wear a wrist-worn accelerometer for seven days that was posted to them. Physical activity information was extracted from 100Hz raw triaxial acceleration data after calibration, removal of gravity and sensor noise, and identification of wear / non-wear episodes. We report age- and sex-specific wear-time compliance and accelerometer measured physical activity, overall and by hour-of-day, week-weekend day and season. RESULTS: 103,712 datasets were received (44.8% response), with a median wear-time of 6.9 days (IQR:6.5-7.0). 96,600 participants (93.3%) provided valid data for physical activity analyses. Vector magnitude, a proxy for overall physical activity, was 7.5% (2.35mg) lower per decade of age (Cohen's d = 0.9). Women had a higher vector magnitude than men, apart from those aged 45-54yrs. There were major differences in vector magnitude by time of day (d = 0.66). Vector magnitude differences between week and weekend days (d = 0.12 for men, d = 0.09 for women) and between seasons (d = 0.27 for men, d = 0.15 for women) were small. CONCLUSIONS: It is feasible to collect and analyse objective physical activity data in large studies. The summary measure of overall physical activity is lower in older participants and age-related differences in activity are most prominent in the afternoon and evening. This work lays the foundation for studies of physical activity and its health consequences. Our summary variables are part of the UK Biobank dataset and can be used by researchers as exposures, confounding factors or outcome variables in future analyses.

Comparison of DNA quantification methodology used in the DNA extraction protocol for the UK Biobank cohort.

BACKGROUND: UK Biobank is a large prospective cohort study in the UK established by the Medical Research Council (MRC) and the Wellcome Trust to enable approved researchers to investigate the role of genetic factors, environmental exposures and lifestyle in the causes of major diseases of late and middle age. A wide range of phenotypic data has been collected at recruitment and has recently been enhanced by the UK Biobank Genotyping Project. All UK Biobank participants (500,000) have been genotyped on either the UK Biobank Axiom® Array or the Affymetrix UK BiLEVE Axiom® Array and the workflow for preparing samples for genotyping is described. The genetic data is hoped to provide further insight into the genetics of disease. All data, including the genetic data, is available for access to approved researchers. Data for two methods of DNA quantification (ultraviolet-visible spectroscopy [UV/Vis]) measured on the Trinean DropSense™ 96 and PicoGreen®) were compared by two laboratories (UK Biobank and Affymetrix). RESULTS: The sample processing workflow established at UK Biobank, for genotyping on the custom Affymetrix Axiom® array, resulted in high quality DNA (average DNA concentration 38.13 ng/µL, average 260/280 absorbance 1.91). The DNA generated high quality genotype data (average call rate 99.48% and pass rate 99.45%). The DNA concentration measured on the Trinean DropSense™ 96 at UK Biobank correlated well with DNA concentration measured by PicoGreen® at Affymetrix (r = 0.85). CONCLUSIONS: The UK Biobank Genotyping Project demonstrated that the high throughput DNA extraction protocol described generates high quality DNA suitable for genotyping on the Affymetrix Axiom array. The correlation between DNA concentration derived from UV/Vis and PicoGreen® quantification methods suggests, in large-scale genetic studies involving two laboratories, it may be possible to remove the DNA quantification step in one laboratory without affecting downstream analyses. This would result in reductions in cost and time to complete the project, allowing generation of genetic data faster and cheaper.

The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

Many common variants have been associated with hematological traits, but identification of causal genes and pathways has proven challenging. We performed a genome-wide association analysis in the UK Biobank and INTERVAL studies, testing 29.5 million genetic variants for association with 36 red cell, white cell, and platelet properties in 173,480 European-ancestry participants. This effort yielded hundreds of low frequency (<5%) and rare (<1%) variants with a strong impact on blood cell phenotypes. Our data highlight general properties of the allelic architecture of complex traits, including the proportion of the heritable component of each blood trait explained by the polygenic signal across different genome regulatory domains. Finally, through Mendelian randomization, we provide evidence of shared genetic pathways linking blood cell indices with complex pathologies, including autoimmune diseases, schizophrenia, and coronary heart disease and evidence suggesting previously reported population associations between blood cell indices and cardiovascular disease may be non-causal.