Approved research

A Genome-Wide Association Study (GWAS) of biological age measures in UK Biobank, with a focus on genetic variations of collagens, elastin and pro-inflammatory cytokines

Lay summary

As we age, we accumulate health problems like medical conditions and/or disabilities. However, the speed at which we accumulate those problems is highly variable. On one hand, some people have already accumulated a high number of health problems at a young age, and they look 'frail' and/or 'older than their age'. On the other hand, some people have an advanced age but live with very few health problems, are 'resilient' and seem 'younger than their age'. The reasons behind this wide variation between age (chronological age) and health problems (biological age) are not well known but there may be genetic reasons. We know that variations in genes that deal with inflammatory reactions in the body have been associated with predisposition to accumulate health problems. However, we also need to consider the environment where those inflammatory reactions take place, which is the so-called 'connective tissue'. The connective tissue is made of proteins such as collagen and elastin. Collagens are the most abundant proteins in humans, and they provide strength and shape to the tissues. In addition, a lot of chemical reactions (including inflammatory reactions) happen on their surface, and many other cells depend on connective tissue for their normal functions. In addition, collagens and elastin form the 'building blocks' of blood vessels, and it is possible that genetic variations in those could have whole-system consequences in terms of resilience or a tendency to accelerated ageing. We can measure accumulation of health problems using indices of multimorbidity (that is, the number of diagnosed medical conditions) and disability (that is, problems performing activities of daily living); in addition, in UK Biobank there are also validated measures of frailty (such as the frailty index or the frailty phenotype). We propose a Genome-Wide Association Study of these biological age measures in UK Biobank in order to gain a better understanding of the genetic determinants of biological ageing in humans. Understanding the genetic determinants of frailty and resilience in middle-aged and older people could have a significant public health impact. Our proposed 3-year project will provide an initial phase for a collaboration between the applicant (Prof. Roman Romero-Ortuno: RRO) and Prof. Ross McManus (Professor of Molecular Medicine at Trinity College Dublin). RRO has access to The Irish Longitudinal Study on Ageing (TILDA, http://tilda.tcd.ie) and the proposed pilot work in UK Biobank will inform further collaborative TILDA research looking at novel markers of resilience and successful ageing.