Investigating five large population-based cohort studies to understand for the precursors of multimorbidity risk.

Lead Research Organisation: Cardiff University
Department Name: School of Medicine


Multimorbidity refers to different diseases being present at the same time in a person. For example, we know that almost half of people with a mental health disorder also have a long-term physical health problem and a third of people with a physical health problem have a psychiatric disorder. Life is often more difficult for people with both physical and psychiatric disorders. They can struggle to get the best possible care and are at risk of living less long.

We don't know enough about why multimorbidity happens. To fully understand why changes in physical and mental health happen over time we need large studies of people whose health has been followed over time. Studies of children are very important because they can tell us about early risks for development of multimorbidity later in life. This is important for creating the best plans to prevent at-risk children developing multimorbidity.
To really understand how multimorbidity develops, studies need to have information about the many important behaviours and events that can influence health. For example, we need to know about someone's living environment (e.g., low income), lifestyle (e.g., lack of exercise) or life events (e.g., stressful experiences).

We know that genes can increase risk of physical and psychiatric disorder. We also know that some groups in society are at greater risk of multimorbidity, such as people of Asian and Minority Ethnic groups and people who live in poverty. We don't currently understand why this is and in this study we aim to get answers by studying the development of physical and psychiatric disorders in children at genetic risk. To understand differences in multimorbidity development in people from different ethnic and socio-economic backgrounds, we need studies in which all these groups are well represented.

If we understand better how multimorbidity develops in different groups in society (people at genetic risk, those from different ethnic and socio-economic backgrounds) this will help doctors give patients care that is matched to their specific needs. It will also help doctors, schools and others prevent multimorbidity in at-risk children in ways that suit their backgrounds best.

Finally, to conduct these studies, a team of researchers with a range of expertise is needed, who together understand the range of physical and psychiatric disorders, as well as how genes, the living environment, life style and life events influence these disorders over time.

We are a team with wide-ranging medical and research expertise in physical and psychiatric disorders. We have brought together five very large studies in which the health of close to 700,000 people has been followed over time. Rich medical data is available, including from medical records. Other important information has also been collected such as on the living environment, lifestyle and life events of these people. Genetic information is also available for all people in these studies.

These studies follow the health over time of both adults and children. We can therefore study how physical and psychiatric disorders happen together in adulthood. Importantly we can then also study the early stages of the development of multimorbidity in children. Because our child and adult samples differ in ethnic and socio-economic background, we can also study if the development of multimorbidity differs for different groups in society. Finally, because we have genetic data we can study how genes influence multimorbidity development in people at risk.

Our study will help us understand how multimorbidity develops and which behaviours and events influence this. What we learn will be important for the prevention of multimorbidity in children who are at risk because of genetic, ethnic or economic reasons. We will create health messages for specific groups in society and this can reduce multimorbidity in at risk groups in the future.

Technical Summary

How can we provide targeted interventions that increase the probability of good long term physical and mental health? 46% of people with a mental health disorder have a long-term physical condition and 30% with a long-term physical condition have a mental health problem. The social and economic cost of this multimorbidity (MM) is substantial.
Understanding the nature of MM requires an approach that maps developmental trajectories, and needs a cross-disciplinary team with wide-ranging clinical and research expertise. Richly phenotyped longitudinal cohorts are needed to address the complex interplay between physical and mental health problems and interactions over time with socioeconomic position (SEP), lifestyle and life events.
Our cross-disciplinary team will bring together a unique resource of five large longitudinal population-based cohorts (total n~679,000), combining genome-wide data with highly detailed information on health, education and premorbid and current exposure factors. We will conduct highly powered analysis of MM trajectories in our adult cohorts, which will guide the study of early life precursors in our child cohorts.
Our cohorts are highly diverse in developmental stage (three multigenerational child cohorts and two adult cohorts); ethnic heritage; and SEP. This allows us to map MM across the lifespan in representative ethnic and socio-economic groups, addressing issues of confounding and bias associated with clinical cohorts, and providing insights to inform tailored interventions.
We will study the trajectories of population subgroups that are at high genetic risk of MM. We will include polygenic risk scores (PRS) for relevant traits in our models and explore genomic Copy Number Variants associated with neurodevelopmental disorders.
We will make our findings readily available to the research community and develop materials that will help a range of stakeholders better support those at elevated risk of MM.


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