Genetic variation in the ASTN2 locus in cardiovascular, metabolic and psychiatric traits: evidence for pleiotropy rather than shared biology

Burt, O., Johnston, K. J.A., Graham, N., Cullen, B. , Lyall, D. M. , Lyall, L. M., Pell, J. P. , Ward, J. , Smith, D. J. and Strawbridge, R. J. (2021) Genetic variation in the ASTN2 locus in cardiovascular, metabolic and psychiatric traits: evidence for pleiotropy rather than shared biology. Genes, 12(8), 1194. (doi: 10.3390/genes12081194) (PMID:34440368) (PMCID:PMC8391428)

[img] Text
248519.pdf - Published Version
Available under License Creative Commons Attribution.

7MB
[img] Text
248519Suppl.pdf - Supplemental Material

462kB

Abstract

Background: The link between cardiometabolic and psychiatric illness has long been attributed to human behaviour, however recent research highlights shared biological mechanisms. The ASTN2 locus has been previously implicated in psychiatric and cardiometabolic traits, therefore this study aimed to systematically investigate the genetic architecture of ASTN2 in relation to a wide range of relevant traits. Methods: Baseline questionnaire, assessment and genetic data of 402111 unrelated white British ancestry individuals from the UK Biobank was analysed. Genetic association analyses were conducted using PLINK 1.07, assuming an additive genetic model and adjusting for age, sex, genotyping chip, and population structure. Conditional analyses and linkage disequilibrium assessment were used to determine whether cardiometabolic and psychiatric signals were independent. Results: Associations between genetic variants in the ASTN2 locus and blood pressure, total and central obesity, neuroticism, anhedonia and mood instability were identified. All analyses support the independence of the cardiometabolic traits from the psychiatric traits. In silico analyses provide support for the central obesity signal acting through ASTN2, however most of the other signals are likely acting through other genes in the locus. Conclusions: Our systematic analysis demonstrates that ASTN2 has pleiotropic effects on cardiometabolic and psychiatric traits, rather than contributing to shared pathology.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ward, Dr Joey and Johnston, Ms Keira and Cullen, Dr Breda and Smith, Professor Daniel and Pell, Professor Jill and Lyall, Dr Laura and Strawbridge, Dr Rona and Lyall, Dr Donald and Graham, Dr Nicholas
Creator Roles:
Strawbridge, R. J.Conceptualization, Writing – original draft
Graham, N.Data curation
Cullen, B.Data curation, Writing – review and editing
Lyall, D. M.Data curation, Writing – review and editing
Ward, J.Data curation
Johnston, K. J.A.Writing – review and editing
Lyall, L. M.Writing – review and editing
Pell, J. P.Project administration
Smith, D. J.Project administration
Authors: Burt, O., Johnston, K. J.A., Graham, N., Cullen, B., Lyall, D. M., Lyall, L. M., Pell, J. P., Ward, J., Smith, D. J., and Strawbridge, R. J.
College/School: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
College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Genes
Publisher:MDPI
ISSN:2073-4425
ISSN (Online):2073-4425
Published Online:31 July 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Genes 12(8): 1194
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
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
302131Understanding the excess risk of cardiometabolic disease in individuals with serious mental illnessJill PellMedical Research Council (MRC)MR/S003061/1HW - Public Health