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

Abstract

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.

Publications

10 25 50
 
Description Input into the National Special Educational Needs and Disabilities (SEND) Review and Autism Strategy Department for Education.
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description Report to Welsh Assembly Parliamentary Event for Rare Disease Day summarizing our research on mental health conditions in people with rare genetic conditions.
Geographic Reach National 
Policy Influence Type Implementation circular/rapid advice/letter to e.g. Ministry of Health
URL https://geneticalliance.org.uk/wp-content/uploads/2021/02/Genetic-Alliance-Wales-CPG-Report-Final.pd...
 
Description ALSPAC 
Organisation University of Bristol
Department Avon Longitudinal Study of Parents and Children (ALSPAC)
Country United Kingdom 
Sector Academic/University 
PI Contribution Enhanced links between research institutions: Cardiff University, Leeds University, Queen Mary University London, Copenhagen University, Exeter University, Wellcome Sanger Institute. Enhanced links between research cohorts Genes and Health (G&H); Born in Bradford (BiB) and Danish Integrative Psychiatric Research (iPSYCH) studies.
Collaborator Contribution The ALSPAC cohort is one of the five research cohorts our Research Collaborative will conduct research in. ALSPAC/ Bristol researchers have made significant contributions to the development of our Research Collaborative grant proposal.
Impact Collaborative grant proposal submitted.
Start Year 2020
 
Description BiB 
Organisation Bradford Institute for Health Research (BIHR)
Department Born in Bradford
Country United Kingdom 
Sector Public 
PI Contribution Enhanced links between research institutions: Cardiff University, Bristol University, Queen Mary University London, Copenhagen University, Exeter University, Wellcome Sanger Institute. Enhanced links between research cohorts Genes and Health (G&H); Avon Longitudinal Study of Parents and Children (ALSPAC), and Danish Integrative Psychiatric Research (iPSYCH) studies. We have called the CNVs in half of the BiB sample (children and parents) already.
Collaborator Contribution The BiB cohort is one of the five research cohorts our Research Collaborative will conduct research in. BiB/ Leeds researchers have made significant contributions to the development of our Research Collaborative grant proposal.
Impact Collaborative grant proposal submitted.
Start Year 2016
 
Description DECIPHer 
Organisation Centre for the Development and Evaluation of Complex Interventions for Public Health Improvement (DECIPHer)
Country United Kingdom 
Sector Public 
PI Contribution Our Research Collaborative has discussed our plans with DECIPHer and thus increased awareness of the role of childhood risk factors for the development of internalizing disorder and cardiometabolic disorder multimorbidity later in life.
Collaborator Contribution DECIPHer will contribute to our Research Collaborative by sharing experiences about prevention and intervention development. DECIPHer is committed to providing expertise in how successful interventions can be developed based on the findings our Research Collaborative will generate. Our Research Collaborative would partner with DECIPHer for future funding to do so. DECIPHer will also provide access to their wide-ranging networks of policy makers, practitioners and young people.
Impact This is a multidisciplinary collaboration which involves mental health, physical health, genetics, epidemiology and intervention development.
Start Year 2012
 
Description DEMISTIFI-Multi Morbidity Consortium 
Organisation University of Nottingham
Country United Kingdom 
Sector Academic/University 
PI Contribution We will enable opportunities for the DEMISTIFI-Multi Morbidity Consortium for further research of genetic risk factors for multi-organ fibrosis in our cohorts.
Collaborator Contribution The DEMISTIFI-Multi Morbidity Consortium will allow us to extend our collaborations and allow us to apply our analytical strategies to new multimorbidity clusters.
Impact Discussions about collaborations
Start Year 2021
 
Description Genes 2 Mental Health Network (G2MH) 
Organisation National Institutes of Health (NIH)
Department National Institute of Mental Health (NIMH)
Country United States 
Sector Public 
PI Contribution Increased awareness of the rick of physical and mental health multimorbidity in people with Copy Number Variation.
Collaborator Contribution Opportunities for collaboration with a large NIMH-led network of international researchers studying rare genetic variation and mental health. The G2MH network also offers opportunities for replication of our findings in a large international data set.
Impact As above
Start Year 2019
 
Description Genes and Health (G&H) Study 
Organisation East London Genes and Health
Country United Kingdom 
Sector Academic/University 
PI Contribution Enhanced links between research institutions: Cardiff University, Leeds University, Bristol University, Copenhagen University, Exeter University, Wellcome Sanger Institute. Enhanced links between research cohorts Avon Longitudinal Study of Parents and Children (ALSPAC), Born in Bradford (BiB) and Danish Integrative Psychiatric Research (iPSYCH) studies.
Collaborator Contribution The G&H cohort is one of the five research cohorts our Research Collaborative will conduct research in. G&H/ Queen Mary University London researchers have made significant contributions to the development of our Research Collaborative grant proposal.
Impact Collaborative grant proposal submitted.
Start Year 2020
 
Description Intellectual Disability and Mental Health: Assessing Genomic Impact on Neurodevelopment (IMAGINE) 
Organisation University College London
Department Institute of Child Health
Country United Kingdom 
Sector Academic/University 
PI Contribution I am an IMAGINE-ID co-investigator, leading the face-to-face phenotyping WP (WP2) of this grant. Insights we gained whilst developing our Research Collaborative proposal have been shared with the IMAGINE-ID team during our investigator meetings.
Collaborator Contribution The IMAGINE-ID team follows young people with genetic conditions linked intellectual disability over time. The insights IMAGINE-ID is generating on these young people's longitudinal development has impacted on our planning of the Research Collaborative project.
Impact The links with the NHS, charities, politicians we have developed as part of IMAGINE-ID are benefitting our Research Collaborative. The collaboration is multidisciplinary, involving mental health, physical health, epidemiology, genetics.
Start Year 2014
 
Description MoBa 
Organisation Norwegian Mother and Child Cohort (MoBa)
Country Norway 
Sector Public 
PI Contribution We have discussed opportunities for collaboration on physical and mental health multimorbidity. Cardiff has advised MoBa researchers on research measures and ethics applications for studying individuals with rare genetic disorders.
Collaborator Contribution MoBA researchers have written letters of support for our Research Collaborative application. If our application is successful, we will work together. This will offer opportunities for future collaborative grant proposals as well as joint research papers.
Impact The collaboration is multidisciplinary, involving mental health, physical health, epidemiology, genetics.
Start Year 2020
 
Description National Centre for Mental Health 
Organisation National Center for Mental Health (NCMH)
Country Philippines 
Sector Hospitals 
PI Contribution The NCMH Director is a collaborator on our Research Collaborative grant. Our Collaborative grant will employ a PPI and Impact Officer. This officer will be embedded within NCMH. This will offer new opportunities for NCMH to be able to link in with the PPI and impact efforts of our project as well as the PPI and impact efforts at the various cohorts that are part of our Collaborative (in particularly the Genes and Health (G&H) cohort at Queen Mary University in London; the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort in Bristol University; and the Born in Bradford (BiB) cohort Leeds University. I am a PI within NCMH.
Collaborator Contribution We will benefit from the extensive expertise on mental health existing within NCMH. We will benefit from the highly successful, vibrant NCMH outreach and engagement activities. Our PPI and impact Officer will work together with this team at NCMH. We have already received input on our PPI and impact grant sections from NCMH. The NCMH Intervention Development Coordinator has been part of and made very useful contributions to the PPI/ impact meetings we have organized to develop the PPI/ impact strategies for our Research Collaborative. NCMH has also facilitated the discussions that we have had about our Collaborative grant proposal with Health Care Research Wales. NCMH will help us with our outreach activities and ensure we reach wide-ranging audiences with our findings, including through podcasts, Youtube, radio, TV, other media.
Impact This is a multidisciplinary collaboration, involving mental health (including intellectual disability), physical health, genetics, PPI, impact. Outputs that have already resulted from this collaboration include input in the Research Collaborative grant proposal, facilitation of links with Welsh Government and opportunities for outreach through the media.
Start Year 2017
 
Description The MINDDS (Maximising Impact of research in Neuro-Developmental DisorderS) COST Pan-EU network. 
Organisation European Cooperation in Science and Technology (COST)
Department COST Action
Country Belgium 
Sector Public 
PI Contribution I am Executive Committee Member and have been Leader of Working Group 2. I have led workshop on rare genetic conditions and mental health for clinicians and researchers throughout the EU.
Collaborator Contribution Our findings on the impact of rare genetic variants on physical and mental health multimorbidity are fed back into MINDDS.
Impact Increased awareness of physical and mental health multimorbidity risk in individuals with rare genetic disorders.
Start Year 2017
 
Description Wolfson Centre for Applied Research 
Organisation Bradford Institute for Health Research (BIHR)
Department Born in Bradford
Country United Kingdom 
Sector Public 
PI Contribution Our Research Collaborative has discussed our plans with the Wolfson Centre for Applied Research and thus increased awareness of the role of childhood risk factors for the development of internalizing disorder and cardiometabolic disorder multimorbidity later in life.
Collaborator Contribution The Wolfson Wolfson Centre for Applied Research will contribute to our Research Collaborative expertise in how health inequalities in young people can be reduced and guidance in which early-years interventions which are most effective.
Impact This collaboration will provide our Research Collaborative with pathways into clinical impact. The collaboration is multidisciplinary, involving mental health, physical health, epidemiology, genetics.
Start Year 2020
 
Description Wolfson Centre for Young People's Mental Health 
Organisation Cardiff University
Department Wolfson Centre for Young People's Mental Health
Country United Kingdom 
Sector Academic/University 
PI Contribution The Cardiff Wolfson Centre has an interest in the longitudinal links between internalizing disorder and physical health disorder. We have agreed that we will have shared seminars, so that the Wolfson Centre stays up-to-date about our findings and that our findings can inform their research strategy. We will also have shared statistical workshops and shared dissemination events.
Collaborator Contribution The two Cardiff Wolfson PIs are collaborators on our Research Collaborative. They have expertise in the development of depression over time in young people which they will bring to our project. They are developing evidence-based interventions for internalizing disorder for young people and at-risk families. They are also developing school-based programs to promote positive mental health in young people. They will share best practice about these programs with us. We will also have shared statistical workshops and shared dissemination events.
Impact The Cardiff Wolfson Centre Directors are collaborators on our Research Collaborative grant proposal. We have discussed common interests together and plan to collaborate. This will be a multidisciplinary collaboration involving mental health, physical health, genetics, epidemiology, intervention.
Start Year 2021
 
Description iPSYCH 
Organisation The Lundbeck Foundation Initiative for Integrative Psychiatric Research
Country Denmark 
Sector Academic/University 
PI Contribution Enhanced links between research institutions: Cardiff University, Leeds University, Queen Mary University London, Bristol University, Exeter University, Wellcome Sanger Institute. Enhanced links between research cohorts Genes and Health (G&H); Born in Bradford (BiB) and Avon Longitudinal Study of Parents and Children (ALSPAC).
Collaborator Contribution The iPSYCH cohort is one of the five research cohorts our Research Collaborative will conduct research in. iPSYCH/ Copenhagen researchers have made significant contributions to the development of our Research Collaborative grant proposal.
Impact Collaborative grant proposal submitted.
Start Year 2020
 
Description Article in Very well health 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Media attention about rare genetic disorders and mental health
Year(s) Of Engagement Activity 2021
URL https://www.verywellhealth.com/autism-diagnosing-criteria-genetic-conditions-5095503
 
Description Department of Education 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Schools
Results and Impact We discussed the plans for our Research Collaborative with the DoE and they wrote a letter to support our project.
Year(s) Of Engagement Activity 2021
 
Description Discussions with Health and Care Research Wales 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact We discussed with Health and Care Wales representatives our plans for our Research Collaborative grant. We received confirmation that proposal was interesting and addressed a clear area of need.
Year(s) Of Engagement Activity 2021
 
Description Discussions with rare chromosome support charity Unique 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact We discussed the plans for our Research Collaborative with Unique and they confirmed this is an important area of research and they wrote a letter to support our project.
Year(s) Of Engagement Activity 2021
 
Description Discussions with support charity CEREBRA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact We discussed the plans for our Research Collaborative with CEREBRA and they confirmed this is an important area of research and they wrote a letter to support our project.
Year(s) Of Engagement Activity 2021
 
Description Genetic Alliance 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact We discussed the plans for our Research Collaborative with Genetic Alliance and they wrote a letter to support our project.
Year(s) Of Engagement Activity 2021
 
Description Lectio Magistralis at the Festival Della Scienza, Genoa, Italy. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Presentation at Science Festival for ~300 people.
Year(s) Of Engagement Activity 2020
 
Description Presentation at 'What I know best' congress, Rome, Italy 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Presentation to Clinical Geneticists and other healthcare workers and those interested in genetics to provide an update of the field
Year(s) Of Engagement Activity 2021
 
Description Presentation at All Wales Medical Genetic Service's Psychiatry & Genetics multidisciplinary team meetings 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation to provide an update on our research findings
Year(s) Of Engagement Activity 2021
 
Description Presentation at rare chromosomal disorder MaxAppeal meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Presentation about our research.
Year(s) Of Engagement Activity 2020
 
Description Radio and television interest 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Media interest about autism risk in individuals with rare genetic disorders. The Cardiff new item was picked up by 29 news sites, and over 40 radio and TV stations including Fox, CBS and ABC news, 4 blogs and had a twitter reach of >60,000 people.
Year(s) Of Engagement Activity 2021
URL https://www.cardiff.ac.uk/news/view/2484687-clinical-criteria-for-diagnosing-autism-inadequate-for-p...
 
Description Wales Gene Park/Genetic Alliance Genomics Cafe 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Purpose: public engagement and to raise awareness about research. Impact: Strengthening of relationship with third sector organisations. Attendees discussed and fed back on research. Participants were recruited into the research project presented on.
Year(s) Of Engagement Activity 2019,2020
URL https://www.walesgenepark.cardiff.ac.uk/2019/05/23/public-genomics-cafe/