Internalising and cardiometabolic multimorbidity in the BiB cohort: Role of genetic variation, biological markers, and ethnic ancestry.

Multimorbidity, also known as Multiple Long-Term Conditions refers to the presence of two or more chronic conditions in a person at the same time. Multimorbidity poses a major challenge to health services and significantly increases the risk of functional disability and reduced life expectancy. The most common type of physical and mental health multimorbidity in older age is between internalising disorders, such as anxiety and depression, and cardiometabolic disorders (such as hypertension, type 2 diabetes and cardiovascular diseases). It is therefore important to better understand how this type of multimorbidity develops over time so that the findings can inform action during the early stages of risk. Risk of both internalising and cardiometabolic conditions tends to start in early life with genetic and environmental factors both contributing. The onset of both internalising and cardiometabolic disorders is known to be associated with inflammatory markers (indicating activity of the immune system) and metabolic markers (telling us about chemical processes within cells).
A range of rare genetic conditions caused by small deletions or duplications on chromosomes (called Copy Number Variants or CNVs) can increase the risk of neurodevelopmental conditions such as learning difficulties, ADHD, and autism. We have recently shown these rare genetic conditions also increase the likelihood of developing internalising and cardiometabolic disorders as well as their multimorbidity in adulthood. However, this research was conducted in a relatively affluent cohort of predominantly European ancestry and of older age (the UK BioBank cohort). We would like to further investigate this risk in a younger and less affluent population and examine whether having a CNV influences risk of multimorbidity of internalising and cardiometabolic differently depending on ethnic ancestry (European or South Asian). Born in Bradford thus provides a unique opportunity to explore this topic.
Both internalising and cardiometabolic disorders have been associated with blood biomarker changes. We aim to compare metabolomic and inflammatory markers in children and mothers with and without CNVs, at different points across development, to understand any additional risk markers of multimorbidity of internalising and cardiometabolic disorders. With a better knowledge of the risk factors for development of these conditions, we hope to inform the development of effective interventions to help reduce this risk.