The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals

Strawbridge, R. J. et al. (2021) The overlap of genetic susceptibility to schizophrenia and cardiometabolic disease can be used to identify metabolically different groups of individuals. Scientific Reports, 11, 632. (doi: 10.1038/s41598-020-79964-x) (PMID:33436761) (PMCID:PMC7804422)

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Abstract

Understanding why individuals with severe mental illness (Schizophrenia, Bipolar Disorder and Major Depressive Disorder) have increased risk of cardiometabolic disease (including obesity, type 2 diabetes and cardiovascular disease), and identifying those at highest risk of cardiometabolic disease are important priority areas for researchers. For individuals with European ancestry we explored whether genetic variation could identify sub-groups with different metabolic profiles. Loci associated with schizophrenia, bipolar disorder and major depressive disorder from previous genome-wide association studies and loci that were also implicated in cardiometabolic processes and diseases were selected. In the IMPROVE study (a high cardiovascular risk sample) and UK Biobank (general population sample) multidimensional scaling was applied to genetic variants implicated in both psychiatric and cardiometabolic disorders. Visual inspection of the resulting plots used to identify distinct clusters. Differences between these clusters were assessed using chi-squared and Kruskall-Wallis tests. In IMPROVE, genetic loci associated with both schizophrenia and cardiometabolic disease (but not bipolar disorder or major depressive disorder) identified three groups of individuals with distinct metabolic profiles. This grouping was replicated within UK Biobank, with somewhat less distinction between metabolic profiles. This work focused on individuals of European ancestry and is unlikely to apply to more genetically diverse populations. Overall, this study provides proof of concept that common biology underlying mental and physical illness may help to stratify subsets of individuals with different cardiometabolic profiles.

Item Type:Articles
Additional Information:IMPROVE was supported by the European Commission (Contract number: QLG1-CT-2002-00896), the Swedish Heart-Lung Foundation, the Swedish Research Council (projects 8691 and 09533), the Knut and Alice Wallenberg Foundation, the Foundation for Strategic Research, the Stockholm County Council (project 592229), the Strategic Cardiovascular and Diabetes Programmes of Karolinska Institutet and Stockholm County Council, the European Union Framework Programme 7 (FP7/2007-2013) for the 10 Innovative Medicine Initiative under grant agreement n° IMI/115006 (the SUMMIT consortium), the Academy of Finland (Grant #110413), the British Heart Foundation (RG2008/08, RG2008/014) and the Italian Ministry of Health (Ricerca Corrente). The UK Biobank was established by the Wellcome Trust, Medical Research Council, Department of Health, Scottish Government and Northwest Regional Development Agency. UK Biobank has also had funding from the Welsh Assembly Government and the British Heart Foundation. Data collection was funded by UK Biobank. This project was completed using UK Biobank applications 6533 (PI. DJS) and 1755 (PI. JPP). RoJS is supported by a UKRI Innovation-HDR-UK Fellowship (MR/S003061/1). LML is supported by the JMAS Sim Fellowship for depression research from the Royal College of Physicians of Edinburgh. AF is supported by an MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/1). KJAJ is supported by an MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh. DJS acknowledges the support of a Lister Prize Fellowship (173096) and MRC Mental Health Data Pathfinder Award (MC_PC_17217). BS is financially supported by the Knut and Alice Wallenberg Foundation as part of the National Bioinformatics Infrastructure Sweden at SciLifeLab.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Smith, Professor Daniel and Cullen, Dr Breda and Graham, Dr Nicholas and Ferguson, Ms Amy and Lyall, Dr Laura and Bailey, Dr Mark and Ward, Dr Joey and Johnston, Ms Keira and Pell, Professor Jill and Lyall, Dr Donald and Strawbridge, Dr Rona
Authors: Strawbridge, R. J., Johnston, K. J. A., Bailey, M. E.S., Baldassarre, D., Cullen, B., Eriksson, P., deFaire, U., Ferguson, A., Gigante, B., Giral, P., Graham, N., Hamsten, A., Humphries, S. E., Kurl, S., Lyall, D. M., Lyall, L. M., Pell, J. P., Pirro, M., Savonen, K., Smit, A. J., Tremoli, E., Tomainen, T.-P., Veglia, F., Ward, J., Sennblad, B., and Smith, D. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > General Practice and Primary Care
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Mental Health and Wellbeing
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Public Health
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Scientific Reports 11: 632
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302131Understanding the excess risk of cardiometabolic disease in individuals with serious mental illnessJill PellMedical Research Council (MRC)MR/S003061/1HW - Public Health
190660MRC Doctoral Training Grant 2013/14 and 2014/15George BaillieMedical Research Council (MRC)MR/K501335/1MVLS - Graduate School
173096Investigating comorbidity between hypertension and bipolar disorder to identify new and repurposed medications for bipolar disorderDaniel SmithLister Institute of Preventive Medicine (LISTININ)Research Prize 2016HW - Mental Health and Wellbeing
302957Mental Health Data PathfinderDaniel SmithMedical Research Council (MRC)MC_PC_17217HW - Mental Health and Wellbeing