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2022-02-27| In-Depth

Big is Beautiful? What We Had Learned From The First 2 Decades of The UK Biobank

by Sahana Shankar
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Harvard Keynote Series on Genomic Medicine

The UK Biobank is one of the earliest and largest databases for biological data. It is a centralized repository from half a million people which enables long-term prospective research into diseases. Integrating genomics into clinical care has remarkably improved disease diagnosis and treatment options in many medical fields such as oncology, cardiology, rare diseases, and infections.

The Harvard International Center for Genetic Disease (iCGD) has organized Harvard Keynote Series on Genomic Medicine features by internationally renowned scientists. For this session, Sir Rory Collins, Chief of the UK Biobank will share the genesis of the Biobank, what they have learned from the past two decades from those data, and how it could be leveraged to uncover new resources for disease prevention.

Rory Collins
Sir Rory Collins, Chief of the UK Biobank

Since 2006, UK Biobank is largely funded by the Wellcome TrustMedical Research CouncilDepartment of HealthScottish Government, and the Northwest Regional Development Agency. This large-scale and collaborative effort hopes to democratize healthcare research and enable scientific discovery. 

The distinguishing feature of the biobank is that the database is maintained from the data generated from prospective cohorts- a large sample set, currently standing at 0.5 million participants, that can be analyzed regularly over a long period of time. This real-time and multi-module access can help understand disease emergence; interaction between multiple risk factors such as lifestyle, environment, and genetics. It allows the development of multiple lines of investigation for multiple diseases, wherein a single disease can be analyzed for many risk factors and one risk factor can be assessed for its involvement in many diseases. 

Value of Going Big

As an example, Sir Collins demonstrated how data collected from a half-million people enabled us to understand the correlation between blood pressure and the risk of coronary heart disease in different age groups. This linkage was not very evident in a sample size of 5,000. At 50,000, there was some correlation, however, the statistical confidence was low. So, the true value of such data comes from long-term data collected from a large sample set. When looking into 500,000 people they started seeing log-linear associations and interactions which you wouldn’t see with data from only 5,000 or 50,000 people.

The database is composed of 500,000 samples from people aged 40-69. This age group is young enough to get them before the disease changes their risk factors and old enough that they will start to produce information within a reasonable of time. The sample group is composed of England (89%), Scotland (7%), and Wales (4%), and complete with medical records, family history, genotyping, biochemical analysis of blood/urine, cognitive function, and body vitals. Some additions such as activity monitoring, genome sequencing, repeat testing, functional imaging have been done based on specific investigations.

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To demonstrate the value of cohort-scale analysis, Sir Collins mentioned the identification of 4 genes associated with dementia, which correlated with micro-bleeds in the brain. These genes were altered in their expression in subcortical regions of the brain and related to iron transport, indicating that the condition could be reversed with medical intervention. 

During the COVID-19 pandemic, Biobank data has been used to develop a pre-infection and post-infection comparison profile of organs which clearly demonstrated the loss of grey matter in brain areas associated with taste and smell, which is consistent with COVID-19 symptoms. 

Pioneering a New Approach to Healthcare

With regular follow-ups and repeat experiments, the data can provide valuable information on genetic and non-genetic determinants of aging, cognitive problems, and terminal diseases. With the UK’s centralized and robust healthcare infrastructure, the database is continuously updated with deaths, disease incidences, hospitalizations, and other medical information for all its participants. 

With the increase in incidences of chronic diseases like diabetes, cancers, and lifestyle conditions like obesity, the database could help identify genetic linkages and risk factors to help the medical community to develop an early diagnosis,  prevention measures, and treatment options. 

Sir Rory Collins and Dr. Alireza Haghighi Director, iCGD
Sir Rory Collins, Chief of the UK Biobank and Dr. Alireza Haghighi, founding Director of the iCGD during the Q&A session

Biobank is available to all researchers involved in healthcare. It has strict selection criteria on the type of assays allowed on samples to ensure maximum returns. The data generated using Biobank samples is verified and audited. The bioinformatics data is hosted on a cloud and available to be analyzed by the scientific community.  With over 3,000 scientists working on different aspects of the sample set and publishing over 4,000 articles in a decade, Biobank has enabled crucial research into the future of health. 

In the future, Sir Collins believes the Biobank will continue to expand its repertoire to include data from multiple avenues such as histopathology, imaging scans, digital apps, participant questionnaires on health and wellbeing, mental health services, etc. AI and machine learning approaches will be incorporated to combine all datasets to build a comprehensive and interactive database. There are upcoming updates on the research analysis platform to help scientists derive more value from the data. It will continue to invite and support researchers to develop tools and resources to advance biomedicine. With its unique combination of breadth, depth, and duration of the assessment, UK Biobank is positioned to accelerate our understanding of health and disease and improve global public health.

 

About iGCD: The iGCD is a platform that focuses on the analysis of patients and healthy subjects from different parts of the world for research into the causes and consequences, prevention, and treatment of disease. The iCGD brings together world-class clinicians and scientists and an unmatched dedication to multidisciplinary research, cutting-edge technology, and innovative methods. The center also implements research, education, and clinical programs to build sustainable capacity in genomic medicine and in genetic research, with the aim of contributing to improved public health. 

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