Biological mechanisms of aging predict age-related disease multimorbidities in patients

Lead Research Organisation: University College London
Department Name: Genetics Evolution and Environment

Abstract

Aim: The aim is to identify common genes and pathways underlying human age-related diseases and shorter human health-span.
Hypothesis: We hypothesise that there are common genes that that are associated with the rate of the ageing process in humans and these genes increase susceptibility to age-related disease and decrease health-span. We hypothesise they reflect the genes frequently associated with ageing in model organisms, although this is controversial (Kirkwood et al., 2011). If common pathological pathways contribute to the ageing process in humans then it is likely that genes detected in GWAS of human health -span and GWAS of age -related disorders will overlap (Johnson et al., 2015; Jeck et al., 2012).
3. Methods of the Project
Analyses will be carried out in R Version 3.3.3. We will build on previous studies in the area (Johnson et al., 2015; Zhu et al., 2016). The project will involve examining the genes that predispose to earlier onset age-related disease by carrying out a health span GWAS using UK Biobank (Fig. 1A). We will also identify common genes between different age-related diseases from the NHGRI-EBI GWAS catalogue (Fig. 1B).The identified genes are likely to be involved in the human ageing process (Fig. 1C).We will assess their overlap with the "druggable" genome (Fig. 1D). We will prioritize druggable genes, if identified. This will be followed by further analysis (Fig. 1E).

The second part of the project will involve assessment of role of eQTLs in age-related disease using Summary-data-based Mendelian Randomization (Figure 5). Therefore, we will identify age-related disease genes that also increase or decrease gene expression (Fig. 5A). We will assess theiroverlap with genes that increase or decrease in expression with age (Fig. 5B). This is based on the hypothesis, that if increased expression of gene is linked to age-related disease and increased expression of the same gene occurs with the ageing process this provides additional evidence that the age-related changes in expression of that gene is involved in the pathogenesis of the disease (Fig. 5C).

Studentship Projects

Project Reference Relationship Related To Start End Student Name
MR/N013867/1 01/10/2016 30/09/2025
1764958 Studentship MR/N013867/1 01/10/2016 30/03/2021 Helen Fraser