The genetic contribution of biological age differences in disease risk (360G-Wellcome-225465_Z_22_Z)

Telomere length (TL) is a biological marker that has previously been linked to biological age, shortening over time. One measure of TL, mean leucocyte TL (LTL) varies highly between individuals and LTL variation has been associated with a wide range of age-related diseases and their risk factors. Some of the LTL and age-related disease have been shown to have a causal relationship, with shorter or longer LTL being causally associated with an increase in disease risk. This has been shown using genetic information via Mendelian Randomisation (MR) and polygenic risk scores. However, it is not yet understood how this causal relationship works and what might be driving this link. I aim to extend the understanding of this causal relationship using UK Biobank data. Here I will extend the investigation by using more complex additional methods, including non-linear relationships. I will also look at multivariate MR, and interaction analyses to determine the direct causal pathways related to disease risk and the role that LTL takes in a wider disease context. This will increase the understanding of the relationship between TL and age-related diseases, which may help to identify new preventative and therapeutic targets.