Understanding the excess risk of cardiometabolic disease in individuals with serious mental illness
Lead Research Organisation:
University of Glasgow
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.
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.
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.
Organisations
People |
ORCID iD |
| Rona Strawbridge (Principal Investigator / Fellow) |
Publications
Broadaway KA
(2023)
Loci for insulin processing and secretion provide insight into type 2 diabetes risk.
in American journal of human genetics
Campbell DD
(2021)
Effects of increased body mass index on employment status: a Mendelian randomisation study.
in International journal of obesity (2005)
Chen J
(2021)
The trans-ancestral genomic architecture of glycemic traits.
in Nature genetics
Coggi D
(2021)
Relationship between Circulating PCSK9 and Markers of Subclinical Atherosclerosis-The IMPROVE Study.
in Biomedicines
Evangelou E
(2018)
Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.
in Nature genetics
Ferguson AC
(2020)
Association of SBP and BMI with cognitive and structural brain phenotypes in UK Biobank.
in Journal of hypertension
Ferri N
(2020)
Sex-specific predictors of PCSK9 levels in a European population: The IMPROVE study.
in Atherosclerosis
| Description | Vacation Scholarship, Investigating the impact of genetic risk for severe mental illness on adipose tissue biology |
| Amount | £2,160 (GBP) |
| Funding ID | VAC-1726-2022, |
| Organisation | Medical Research Scotland |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 05/2022 |
| End | 08/2022 |
| Title | Repurposing quality control methods for precision medicine |
| Description | Multi-dimensional scaling (MDS), typically used to identify population outliers based on genetic data, was used to subset individuals into 3 groups. Between-group differences suggest that this approach has potential applications for precision medicine. Genetic variation was selected based on prior evidence for association with the traits of interest, and the standard procedure for MDS was conducted. Visual inspection of the discovery dataset identified 3 groups of individuals. Validation of the method and sensitivity analyses were conducted in a second, independent dataset. Finally, a larger replication dataset was used, with consistent identification of 3 groups of individuals. During the publication process, additional methods that can automate the identification of groups (rather than relying on visual inspection) provided further validation of the groups. In summary, this method demonstrated robust findings over 3 separate datasets. Between groups differences were statistically, but not clinically, significant, however the high risk cohort demonstrated greater between-group differences. Further work to improve efficiency of the method and investigate the clinical potential is ongoing. |
| Type Of Material | Model of mechanisms or symptoms - human |
| Year Produced | 2020 |
| Provided To Others? | Yes |
| Impact | None so far known. |
| Title | Genetics of self-reported risk-taking behaviour, trans-ethnic consistency and relevance to brain gene expression |
| Description | A genome wide association study investigating risk taking behaviour |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| URL | http://researchdata.gla.ac.uk/id/eprint/929 |
| Title | Genome-Wide Association Study of Circadian Rhythmicity in 71,500 UK Biobank Participants and Polygenic Association with Mood Instability |
| Description | A series of genome wide association studies investigating Circadian Rhythmicity. Please see also the readme files located inside each zip file. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| URL | http://researchdata.gla.ac.uk/id/eprint/928 |
| Title | Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide |
| Description | A series of genome wide association studies investigating suicidality and self-harm |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| URL | http://researchdata.gla.ac.uk/id/eprint/930 |
| Title | Novel genome-wide associations for anhedonia, genetic correlation with psychiatric disorders, and polygenic association with brain structure |
| Description | A genome wide association of anhedonia |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| URL | http://researchdata.gla.ac.uk/id/eprint/926 |
| Title | Sex-Stratified Genome-Wide Association Study of Multisite Chronic Pain in UK Biobank |
| Description | Summary statistics from the sex-stratified genome-wide association study of multisite chronic pain in UK Biobank |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | I am unaware of impact, however as the data is freely available to other researchers, there might be impact that I am unaware of. |
| URL | http://researchdata.gla.ac.uk/id/eprint/1050 |
| Title | Summary statistics from a genome-wide association study of carotid intima-media thickness in UK Biobank. |
| Description | Summary statistics from a genome-wide association study of carotid intima-media thickness in UK Biobank, available publicly to enable follow-up analyses/comparisons with other data. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2021 |
| Provided To Others? | Yes |
| Impact | None that I am aware of, though as this data is freely available, other researchers might have had impact from this data that i am unaware of. |
| URL | http://researchdata.gla.ac.uk/id/eprint/1170 |
| Title | The genomic basis of mood instability: identification of 46 loci in 363,705 UK Biobank participants, genetic correlation with psychiatric disorders, and association with gene expression and function |
| Description | A genome wide association study of mood instability |
| Type Of Material | Database/Collection of data |
| Year Produced | 2019 |
| Provided To Others? | Yes |
| URL | http://researchdata.gla.ac.uk/id/eprint/927 |
| Description | Centro Cardiologico Monzino |
| Organisation | Monzino Cardiology Center |
| Country | Italy |
| Sector | Hospitals |
| PI Contribution | I manage a dataset that is jointly owned by CCM and Karolinska Insitutet. This involves securely storing the data, updating as and when required and sharing the data. For genetic studies using this data I am consulted for design and analysis input. I conduct my own studies on the data, in collaboration with all partners. The Italian partners sent a PhD student to our group to learn from me how to conduction and interpret genetic studies (2019). |
| Collaborator Contribution | The partners in Italy were instrumental in setting up the collaboration and collection of the data. They continue to work with the data, both to improve the coverage and depth of data, but also to conduct studies on the data. |
| Impact | This collaboration is multidisciplinary, including clinical, epidemiological, statistical and genetic components. Outputs from this collaboration are primarily scientific papers, typically 5-10 a year for the collaborative group. |
| Start Year | 2019 |
| Description | Collaboration with St. Jude Children's Research Hospital |
| Organisation | St Jude Children's Hospital |
| Country | United States |
| Sector | Hospitals |
| PI Contribution | Dr Joelle Magne contacted me as a recognised researcher in human complex disease genetics, to add a human genetics component to her project. |
| Collaborator Contribution | I have designed and conducted analyses of UK Biobank data in order to demonstrate any human relevance of her experimental study. For this part of the project I have drafted the methods and interpreted the results for the mansucript that is under preparation. The manuscript describes an exciting advance in understanding how autophagy contributes to cardiovascular disease, and uses a collection of complimentary state-of-the-art methods, and is likely to result in a high impact publication. |
| Impact | Manuscript in preparation Abstract submitted to a conference on autophagy. |
| Start Year | 2022 |
| Description | International collaboration on the GENIAL dataset |
| Organisation | University of Copenhagen |
| Department | NNF Center for Basic Metabolic Research |
| Country | Denmark |
| Sector | Academic/University |
| PI Contribution | Professor Loos (Copenhagen) and Dr Witteman (Oxford) apporached the GENIAL study for analyses to compliment thier ongoing project. As the analyst of this unique dataset, i am conducting analyses that will be added to an ongoing project with exciting results from a variety of methods that should result in a very high impact publication. |
| Collaborator Contribution | We will be contributing time/expertise/a unque dataset and thus unique results. |
| Impact | Noe so far |
| Start Year | 2023 |
| Description | International collaboration on the GENIAL dataset |
| Organisation | University of Oxford |
| Department | Big Data Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Professor Loos (Copenhagen) and Dr Witteman (Oxford) apporached the GENIAL study for analyses to compliment thier ongoing project. As the analyst of this unique dataset, i am conducting analyses that will be added to an ongoing project with exciting results from a variety of methods that should result in a very high impact publication. |
| Collaborator Contribution | We will be contributing time/expertise/a unque dataset and thus unique results. |
| Impact | Noe so far |
| Start Year | 2023 |
| 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 | Research Institute of Hospital de la Santa Creu I Sant Pau |
| Organisation | Hospital de Sant Pau |
| Country | Spain |
| Sector | Hospitals |
| PI Contribution | I set up a collaboration with Dr Maria Sabater-Lleal to enable follow-up of findings from two seperate projects. We applied for MRF funding but the application was rejected (2021). The planned work is the included in additional funding applications (outcome not yet known) to the Wellcome trust and the British HEart Foundation. Further opportunities for funding for this collaboration are being investigated. |
| Collaborator Contribution | We jointly wrote the application for funding. Maria would bring expertise and access to certain datasets that I lack. |
| Impact | Grant applications (1 was rejected, 2 outcomes pending). |
| Start Year | 2021 |
| Description | Blog highlighting wasy health data is being used to advance understanding of mental illness |
| 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 | HDR-UK focused on me and my research as an example of how health data is being used currently to further understanding of mental illness and its comorbiditites. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.hdruk.ac.uk/news/meet-the-future-leaders-in-mental-health-data-science/ |
| Description | Festival of Genomics |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Industry/Business |
| Results and Impact | Oral presentation of my work on genetics of suicidality, which represents a huge step forward in understanding the biology of suicidal behaviour, at the Festival of Genomics, London, 2020. The purpose of the meeting was to highlight recent advances in some of the pressing issues facing the UK medical/medical research community. It was attended by researchers, clinicians, educational bodies, industry partners, policy makers. As a result of the social media (Twitter) advertising in advance of the meeting, 3 companies requested meetings to discuss potential opportunities. Since the advertising for this/the presentation, I have had increased activity on twitter (relating not only to the publication on Suicidality). |
| Year(s) Of Engagement Activity | 2020 |
| URL | https://www.frontlinegenomics.com/interview/28816/interview-with-dr-rona-strawbridge-ukri-innovation... |
| Description | Festival of genomics and biodata 2021 |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | A talk and Q+A session at the Festival of Genetics and Genomics, on the topic of my latest research paper which used genetics of psychiatric illness to identify 3 groups of individuals with different cardiometabolic risk profiles. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://twitter.com/RJStrawbridge/status/1347235209914290176/photo/1 |
| Description | HDR UK Blog, 2021 |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | A blog post, following on from the Festival of Genomics conference. Gives an overview of my research area and some of my findings. |
| Year(s) Of Engagement Activity | 2021 |
| URL | https://www.hdruk.ac.uk/news/can-genetics-help-us-to-understand-why-people-with-severe-mental-illnes... |
| Description | HDR-UK alumni network blog |
| Form Of Engagement Activity | Engagement focused website, blog or social media channel |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Schools |
| Results and Impact | I wrote an article summarising my career to date, for HDR-UK's alumni network website, which aims to highlight a variety of ways in which health data science contributes to sucessful careers. The target audience is schools and students. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.hdruk.ac.uk/careers-at-the-cutting-edge-dr-rona-strawbridge/ |
| Description | Infographic for mental health week campaign 2022 |
| 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 | Me and my research was a key part of an infographic produced by HDR-UK, to highlight how health data is being used to advance understanding of mental illness and associated comorbidities. the infographic was hosted on the HDR-UK website for the mental health awareness campagin, which had 3000 visitors during that week. The infographic was widely shared by myself, HDR-UK and my connections on social media (gainaing 3000 impressions that week). The infographic was also highlighted by Today Post Times (a new outlet), which gained an additiional 229 website views and 1839 impressions on twitter during that week. |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.hdruk.ac.uk/wp-content/uploads/2022/09/HDR-UK-How-Health-Data-is-Used-for-Mental-Health.... |
| Description | Podcast for mental health awareness week 2022 |
| 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 | Podcast with a host, someone with lived experience and myself as the mental health researcher, in association with HDR-UK and MQ datascience, a high profile mental health charity, for thier mental health awareness campaign in October 2022. The purpose was to highlight the biological link between physical illness, from both research and personal perspectives. This area is not widely appreciated, leadng to stigma (for example for being overweight), and sub-optimal care (considering medication interactions/variations and response). The podcast was recorded and released as a audio podcast as well as a audio-visual youtube video. Tha campaign website (one place in which the podcast was hosted) had 3000 visitors and the podcast has been downloaded 357 times during the campaign week (the number of downloads since have not been recorded). Overall, the campaign reached an international and diverse audience of 300,000 people |
| Year(s) Of Engagement Activity | 2022 |
| URL | https://www.mqmentalhealth.org/mq-open-mind-podcast-mental-illness-and-physical-disease/ |
| 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 | Request for expert opinion (Daily Record journalist) |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | A journalist requested an expert opinion on suicidal behaviour for an article about Kurt Cobains death. I provided a statement, to be quoted in the article. The journalist quoted me verbatim and followed my requests to change the wording of some components of the article. The article was appropriate. Unfortunately, the headline was terrible/sensationalist. There was an immediate and unsurprising Twitter response. I responded agreeing that the headline was misleading and directing people to the article on our research in The Conversation. This was well received. |
| Year(s) Of Engagement Activity | 2019 |
| URL | https://www.pressreader.com/uk/daily-record/20191112/281883005161541 |
| 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 |