Investigating the Genetic Basis of Human Intrinsic Capacity
Background and rationale: The conceptual roots of human intrinsic capacity (IC) can be traced to the theory of philosopher Martha Nussbaum. In the 2015 annual report on Ageing and Health, the World Health Organisation (WHO) introduced the concept of IC and defined healthy ageing as a function of IC (internal factors related to body and mind) and the environment.
IC is a genetically predetermined trait, but influenced by a range of environmental stimuli and attains a peak value in early adulthood, evolved as adaptive process throughout life and start to decline as age increases. Starting from pregnancy and throughout our life course, there is a continuous interaction of our genes with a range of environmental exposures, impacting physical and mental wellbeing that ultimately determine our IC. Thus, whether people fully achieve the things that they have reason to value will be determined by their IC, which is inherited and then modified by environmental factors through gene-environment interactions. However, evidence on how genetic and environmental factors come together to influence IC is lacking and no study is yet available.
Research questions: How human IC does changes across the life span and how does it impact healthy ageing and mental wellbeing? How much is the role of genetic and environmental factors influencing human IC? To answer these questions, first, a factor analysis method will be applied to compute index score for the general factor-IC and each of the five subdomains: cognitive, sensory, locomotor, vitality and psychological domains. Next, by applying innovative genomic research methodologies and using big biobank data from the UK Biobank (N=500,000) and the LifeLines cohort (N=167,000), the heritability of IC will be estimated followed by the identification of genetic markers and characterisation of biological pathways associated with IC. Further, gene to environment (G x E) interaction analysis will be employed to assess the contribution of environmental factors to IC.
Project duration: This project is expected to be completed in 3 years.
Impact: Knowledge gained from this project can be used as a basis for developing an improved and cost-effective health interventions, broadly applicable around the world to promote healthy ageing and general wellbeing, making the project directly related to the current agenda of international organisations such as WHO.