Source: University of Edinburgh.
More than one thousand people have had their entire genetic make-up decoded as part of a long-term study to gain insight into why some people’s brains age better than others.
Researchers at the University of Edinburgh have completed whole-genome sequencing for more than 1,300 participants in the Lothian Birth Cohorts, a long-running study of cognitive ageing. By combining rich, decades-long cognitive testing with full genetic information, the team aims to uncover genetic contributors to healthy brain ageing and the factors that influence differences in cognitive decline between individuals.
Memory study
The Lothian Birth Cohorts consist of two groups born in 1921 and 1936. Members were originally tested on mental ability at age 11 as part of historical educational surveys, and many have been re-assessed repeatedly in later life. Over the past 15 years researchers from the Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE) at the University of Edinburgh have carried out follow-up cognitive tests, collected blood samples and conducted brain imaging in cohort members, creating a comprehensive longitudinal dataset for studying cognitive change across the lifespan.
Aging brain
Because the cohorts include early-life cognitive measures as well as repeated assessments in older age, they provide an unusually powerful resource for separating lifelong influences from effects that emerge in later life. The combination of cognitive test scores, biological samples and brain scans allows investigators to study how genetic variation relates to trajectories of memory, reasoning and other cognitive abilities, and how genes interact with lifestyle and environmental factors to shape brain health.
Genome sequencing
The recent sequencing project has produced full genomic data for over 1,300 cohort members. Researchers will link these genome sequences with the wealth of existing phenotype data — cognitive performance across decades, clinical and biochemical measures, and neuroimaging — to search for genetic variants and patterns associated with better or worse cognitive ageing. Such analyses may highlight genes, pathways and biological mechanisms involved in preserving memory and thinking skills into older age.
“This genetic data will prove invaluable for understanding why some people’s brains and thinking skills age better than others. The flip side of having such comprehensive genetic data is that we will also understand better how the environment and lifestyle choices can contribute to healthy ageing,” said Professor Ian Deary, Director of the Centre for Cognitive Ageing and Cognitive Epidemiology.
Falling cost
When participants were first recruited to the Lothian Birth Cohorts, sequencing a single person’s genome would have cost around US$100 million. Advances in technology and infrastructure have driven that cost down dramatically: today sequencing a full genome is on the order of US$1,000 (approximately £700). This reduction in cost has made large-scale studies such as this feasible and has accelerated the pace at which population-level genomic resources can be assembled and analysed.
Edinburgh Genomics
The sequencing was carried out at Edinburgh Genomics, one of the UK’s largest sequencing facilities, based at the University of Edinburgh. The project was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and benefited from investments made through the Scottish Genomes Partnership. Rapid sequencing capability and high-quality data output were made possible by the facility’s advanced equipment and experienced technical team.
“This pioneering work has been made possible by our highly skilled team and the Scottish Genomes Partnership’s investment in equipment that enables rapid sequencing and delivery of high quality data at a viable cost,” said Joel Fearnley, Chief Operating Officer at Edinburgh Genomics.
The initiative also reflects broader collaboration between institutions: a major investment in sequencing technology by the Universities of Edinburgh and Glasgow helped establish the Scottish Genomes Partnership and expand national capacity for large-scale genomic research.
Professor David Hume, Director of the University’s Roslin Institute where the sequencing facility is housed, noted the broader potential of the infrastructure, saying the achievement opens the door for similarly sized projects in other species and areas of research. Professor Tim Aitman, Co-Chair of the Scottish Genomes Partnership and Director of the Centre for Genomic and Experimental Medicine, highlighted the potential clinical benefits: “This tremendous rate of genetic sequencing is a testament to an incredible team effort which will accelerate our work towards radically improving disease diagnosis and management of patients in the Scottish NHS.”
Funding: The Lothian Birth Cohorts are funded by Age UK and the Medical Research Council.
Source: University of Edinburgh
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