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)
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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: | Smith, Professor Daniel and Cullen, Dr Breda and Graham, Dr Nicholas and Lyall, Dr Laura and Ward, Dr Joey and Johnston, Ms Keira and Pell, Professor Jill and Strawbridge, Dr Rona and Lyall, Dr Donald |
| 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 > School of Health & Wellbeing > Mental Health and Wellbeing College of Medical Veterinary and Life Sciences > School of Health & 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 |
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Funder and Project Information
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