Understanding the excess risk of cardiometabolic disease in individuals with serious mental illness

Lead Research Organisation: University of Glasgow
Department Name: College of Medical, Veterinary &Life Sci

Abstract

People with serious mental illness (such as schizophrenia, bipolar disorder and depression) die 15-20 years younger than the general population, typically due to heart disease. People with serious mental illness frequently have low socioeconomic status, sedentary lifestyles, poor diets and smoking is common. All of these are recognised risk factors for heart disease. In addition, some medication used to treat symptoms of serious mental illness increase the risk of weight gain and diabetes, further increasing the risk of heart disease. It is unclear whether these risk factors are the reason for the increased risk of heart disease in those with serious mental illness, or whether the biology of serious mental illness overlaps with the biology of heart disease.
Many variations in an individual's DNA (genetic material) are known to increase the risk of serious mental illness. This project will firstly investigate whether these variations also have an effect on diabetes and heart disease. Secondly, this project will determine whether these variations are able to identify people with highest risk of heart disease. Finally, this project will examine whether low socioeconomic status and lifestyle factors have an even great effect on heart disease risk when combined with these genetic variations.
The results of this project will improve understanding of how serious mental illness develops. If the biology of serious mental illness overlaps with heart disease, then drugs used to treat heart disease might be improve treatment for serious mental illness. If DNA variations linked to serious mental illness can improve prediction of heart disease risk or do interact with socioeconomic or lifestyle factors, then heart disease risk can be better managed, by individuals, doctors and policy-makers.

Technical Summary

An urgent question facing health researchers is why individuals with serious mental illness have not benefited in recent advances in cardiovascular prevention. My research investigates possible reasons for this by combining health, genetic and social/lifestyle data with statistical and genetic approaches. Firstly, I will determine whether there are common mechanisms underlying the increased risk of cardiometabolic disease in people with mood disorders. Secondly, I will assess the extent to which low socioeconomic status interacts with these mechanisms. Finally, I will explore whether genetic predisposition to serious mental illness can identify subsets of individuals with distinct cardiovascular risk profiles.
I will utilise European research cohorts, as well as real-world data. The research cohorts (specifically the IMPROVE (European high cardiovascular risk cohort) and PROCARDIS (European coronary artery disease case-control) studies) have been extensively phenotyped for cardiometabolic metabolic variables. The real-world data (specifically PsyCIS (an ongoing study of >10,000 individuals with serious mental illness and/or psychosis within the NHSGGC Safe Haven) and UK Biobank (a population study of ~500,000 individuals with genetic, clinical and lifestyle/social data as well as linkage to NHS records) allow for long-term follow-up. The UKBiobank is particularly valuable for analyses of lifestyle and socioeconomic data. Standard genetic and epidemiological methods will be used for objectives 1 and 2 respectively. Objective 3 will repurpose quality control methodology in an innovative manner.
 
Description KI-Medicine Huddinge 
Organisation Karolinska Institute
Department Department of Medicine, Huddinge
Country Sweden 
Sector Academic/University 
PI Contribution I manage the genetic data for the GENIAL dataset. I provide advice on design and interpretation of genetic studies to Professor Peter Arner and Dr Ingrid Dahlman (Unit for Endocrinology and Diabetes). I have been co-applicant for funding for PhD students that Ingrid has applied for, whereby I would be a co-supervisor for the student. As I have an affiliation with Karolinska Institute (the Cardiovascular Medicine group), This is an informal collaboration. Whilst this collaboration was initiated before the funding was awarded, it is crucial to the research being funded by this award. The application for the award would not have been possible without this collaboration.
Collaborator Contribution I am able to utilise GENIAL genetic and phenotypic dataset for my research, which provides unique phenotyping and therefore ability to address questions in my research that would otherwise not be possible. I have access to the expertise of the group, who are world-leaders in adipose tissue biology and the impact it has on cardiometabolic diseases from basic biology and clinical perspectives. Ingrid is a co-aplicant on an application for a MRC DTP fellowship, whereby she would be a co-supervisor for the student and the student would conduct some of the PhD research in Ingrids lab.
Impact Publications
Start Year 2017
 
Description KI-Medicine Solna 
Organisation Karolinska Institute
Department Department of Medicine, Solna
Country Sweden 
Sector Academic/University 
PI Contribution Through this collaboration I manage the genetic and phenotypic datasets for a number of the datasets owned by Professor Anders Hamsten, Professor Ulf deFaire and Dr Bruna Gigante at Karolinska Institue. This enables deeper investigation of some research questions than otherwise possible, due to the extensive and detailed phenotyping available in these datasets. In addition I provide advice and support in studies that require gnetic analysis to members of the Cardiovascular Medicine group lead by Professor Per Eriksson. As I have a continued affiliation with this group the collaboration is informal. Whilst this collaboration was initiated before the funding was awarded, it is crucial to the research being funded by this award. The application for the award would not have been possible without this collaboration.
Collaborator Contribution Through this collaboration I am able to utilise the PROCARDIS, SCARFSHEEP and IMPROVE datasets for my research. As importantly, I have access to the expertise of the Cardiovascular Medicine group. This is wide ranging, from basic biology to clinical practice in cardio-metabolic disorders.
Impact Publications including:
Start Year 2017
 
Description Popular science article for The Conversation website, then shared through Twitter and Facebook 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact An article about our new study was written for The Conversation, which was then promoted on Facebook and Twitter.
After a week, the article had 5 comments and 37,203 reads on The Conversation.
The article had been republished in The Independent newspaper.
The Facebook audience is limited to my friends and family, which spans a wide range of geographical locations, nationalities and educational backgrounds. Some audience members are scientists, many are not. In the first 24 hrs of being on Facebook this post had 21 interactions/comments.
The Twitter audience is not limited to my personal contacts, rather it is open to all sectors. After a week this post had been retweeted 40 times with 11,315 reads and a handful of questions. Of note, this work was retweeted by a funding body (HDR-UK), my university (University of Glasgow), the cohort used in the study (UKBiobank) and a patient and carere support/advocay group (A Caring Mind).

The questons posed on Twitter/Facebook/The Conversation highlight that these findings are ground breaking, for example:
"there is a strong tendency towards social explanation - sometimes to the point of possible genetic causes being simply dismissed......The current article would be more evidence of the need for that change."
Year(s) Of Engagement Activity 2019
URL https://theconversation.com/what-our-new-study-reveals-about-the-genetics-and-biology-of-suicidal-be...
 
Description University of Glasgow Mental Health and Wellbeing conference. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact This is an annual meeting open to researchers, clinicians and practicioners, Glasgow City HSCP, Graeme Anderson House, patient advocate groups and the general public, aimed at demonstrating some of the resaerch going on in the department to a wider audience. Approximately 60 people atended. I presented some of our work on the genetics of suicidal behaviour. There were 5 questions after the talk which promted some discussion around data availability and translation to clinical practice.
Year(s) Of Engagement Activity 2018