The role of genomic markers of ageing for the risk of metabolic disease (360G-Wellcome-109150_Z_15_A)

Background: The risk for many common complex diseases, including type 2 diabetes, increases with age. Technological advances have recently enabled large-scale investigation of genomic markers of ageing in population-based studies. Whether genomic ageing contributes to the age-related rise of diabetes and related metabolic disorders is unknown. Aim: To systematically identify and study genomic markers of ageing, including telomere length, DNA methylation, and chromosome loss, and investigate their causal roles for morbidity and mortality from type 2 diabetes and other common complex diseases. My overall aim will be achieved by addressing the following specific objectives: Objectives: 1. To perform a systematic literature review of genomic markers of ageing to identify determinants and consequences and assess methods for their characterisation in epidemiological studies. 2. To identify and characterise genetic and modifiable behavioural and environmental risk factors of genomic ageing in large-scale population-based studies. 3. To investigate causal roles of genomic markers of ageing for morbidity and mortality from ageing-related diseases using Mendelian randomization methods, and conduct exploratory studies of the underlying pathways through detailed metabolomic characterisation.