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Using gene knowledge for medical, social and economic benefit. David Porteous, Principle Investigator for Generation Scotland, and an advisor for the Generation Scotland gateway on Wellcome Open Research, tells us about Generation Scotland, and the value its new gateway provides for researchers and the community.  

It has been nearly 20 years since I left the safety net of core funding at the MRC Human Genetics Unit, Edinburgh to join the University of Edinburgh. The incentive for this had much to do with Generation Scotland.

The support for this concept came from Colin Bird, Dean of Medicine, University of Edinburgh and the then Chief Medical Officer for Scotland, David Carter. I spent the next year or so sharing the idea with Medical School colleagues in Edinburgh, Glasgow, Dundee and Aberdeen and NHS Scotland.

The genetic revolution

We chose to do this, as the genetics revolution was well and truly underway. The human genome would soon be sequenced and the cost of wholesale genetic analysis would soon make it feasible and affordable at scale. But what made doing so in Scotland particularly attractive? NHS Scotland has led the way in the UK, with the systematic collection of medical records using a common identifier and making these data available for research.

Importantly, the Scottish population is stable and homogenous, with a strong tradition of supporting medical research. It is also relatively unhealthy, meaning plenty of cases to study. So, the idea was hatched for a population and family based study of genetic and environmental determinants of health, Generation Scotland.

First, we undertook an extensive period of consultation and engagement with stakeholders and the public. This shaped the study and established a strong and robust ethics and governance framework that has stood us in good stead. We then undertook a pilot study recruiting 2,000 participants with Scottish grandparents.

We also worked with the Scottish National Blood Transfusion Service, to bank a representative set of 5,000 donor bloods to serve as anonymised controls for genetic association and genomic architecture studies. But the core of Generation Scotland is the Scottish Family Health Study, comprising 24,000 adults in 7,000 family groups. They were recruited between 2006-2011, mainly from Glasgow, Tayside and latterly Aberdeen.

Participants gave broad consent for genetic studies, approved linkage to their NHS health records and agreed to recontact to participate in follow up studies. They answered 400 health related questions, attended a clinic where 150 clinically relevant measures were made, and donated samples of blood and urine. You can find out more about the cohort and the research findings on our website.

Generation Scotland operates a managed access policy and is open to bona fide researchers, academic and industrial, for medically relevant research within our ethics and governance principles. We have had over 300 requests for access and research using Generation Scotland data and samples, which has resulted in over 200 research papers to date. More information on these publications can be found on our website.

Raising awareness

Why then the Wellcome Open Research Gateway? We want more researchers to be aware of  Generation Scotland as a potential platform for their research. The Gateway will give new users a good feel for how the cohort might be able to support their research. Useful research does not always find an easy and accessible home in specialist journals, yet can be of real value to others in scoping and planning their research. WOR meets that objective. And WOR and Generation Scotland share the same philosophy of open access publication as a public good.

Long-term research   

Our recent study ‘Assessment of dried blood spots for DNA methylation’ by Walker et al illustrates these points. It demonstrates that methylation assays on archived blood spots, prepared at the time of collection closely mimic assays performed on freshly prepared whole DNA. This lays out a pathway to more ambitious epigenomic studies in the future.

“Guthrie card” neonatal blood spots have been routinely collected in Scotland since 1965. There are about 3 million in total, accruing by 60,000 per annum, and are safely stored by NHS Scotland. There is currently a moratorium on research access, but this is under review by the Scottish Government. Generation Scotland is supporting that process. Our feasibility study points to the potential value for predictive health and personalised medicine.

I wanted to end by highlighting an earlier WOR paper on the Gateway, ‘Electronic health record and genome-wide genetic data in Generation Scotland participants’ by Kerr et al. It nicely demonstrates the founding premise from 20 years ago that genome-wide genotyping at scale would be possible and affordable and that NHS records could substitute for expensive clinical investigations.

In the 13 years since recruitment began, Generation Scotland has accumulated 180,000 person years’ worth of NHS health data. This data includes ICD (International Statistical Classification of Diseases and Related Health Problems) codes for prevalent and incident disease, routine biochemistry and prescribing data. Coming soon will be primary care data and hospital based imaging.

Participants can provide additional information remotely, e.g. lifestyle questionnaires and/or by sign-up to clinical studies, e.g. dementia research. Generation Scotland is thus a dynamic and longitudinal study, regularly updated with NHS Scotland data, new phenotyping and -omics annotations. Funding dependent, we aim to expand the cohort to include more family members and the younger generation.

Keep an eye on the Gateway for more news!