Approved Research

Predictive models for healthy ageing based on combined genetic, molecular, and environmental risk factors

Lay summary

Scientific Rationale

As elderly population increases throughout the world, we are faced with unprecedented challenges and opportunities: will we reap the benefits of longer social and economic productivity, or faced with the debilitating socioeconomic cost of disability and dependency?

Understanding the basis of healthy ageing will allow us to better navigate this uncharted territory through strategic health interventions. However, longevity and healthy ageing remain to be one of the most complex phenotypes studied to date. Various factors contribute to its complexity, such as the interplay between risk vs protective risk factors, between genes and environment interactions, and inter-ethnic differences.

Aims

To entangle this complexity and draw statistically-sound conclusions, we will utilise the impeccably large and high-quality UK BioBank dataset to:

* Identify the key genetic, molecular, and environmental determinants of healthy ageing, defined as the combination of longevity, delayed onset of common diseases, and maintenance of physical/cognitive functioning

* Develop predictive models, using genetic polygenic risk scores and relevant biomarker/environment/lifestyle variables, to predict and stratify patients on healthy vs unhealthy ageing trajectories

Duration

Based on the expected computational and scientific complexity of the research project, we expect initial project duration of 3 years.

Public Health Impact

The outcome of this project will have the following public health impacts:

* Identification of individuals with a higher risk of poor ageing trajectories

* Personalized intervention targets (molecular or environmental) for lowering the risk/onset of specific age-related disease of loss-of-function endpoints

* Designing better physical and social infrastructure that might foster better health and wellbeing in older age, through a better understanding of the factors that promote healthy ageing

* Development of methods and computational infrastructure to apply this analysis for other endpoint-of-interest in the UK BioBank resource.