Polygenic risk for schizophrenia, brain structure and environmental risk in UK Biobank

Zhu, X., Ward, J. , Cullen, B. , Lyall, D. M. , Strawbridge, R. J. , Smith, D. J. and Lyall, L. M. (2021) Polygenic risk for schizophrenia, brain structure and environmental risk in UK Biobank. Schizophrenia Bulletin Open, 2(1), sgab042. (doi: 10.1093/schizbullopen/sgab042)

Abstract

Schizophrenia is a heritable neurodevelopmental disorder characterized by neuroanatomical changes in the brain but exactly how increased genetic burden for schizophrenia influences brain structure is unknown. Similarly, the impact of environmental risk factors for schizophrenia on brain structure is not fully understood. We investigated how genetic burden for schizophrenia (indexed by a polygenic risk score, PRS-SCZ) was associated with cortical thickness (CT), cortical surface area (SA), cortical volume (CV) and multiple subcortical structures within 18,147 White British ancestry participants from UK Biobank. We also explored whether environmental risk factors for schizophrenia (cannabis use, childhood trauma, low birth weight and Townsend social deprivation index) exacerbated the impact of PRS-SCZ on brain structure. We found that PRS-SCZ was significantly associated with lower CT in the frontal lobe, insula lobe, lateral orbitofrontal cortex, medial orbitofrontal cortex, posterior cingulate cortex and inferior frontal cortex, as well as reduced SA and CV in the supramarginal cortex and superior temporal cortex, but not with differences in subcortical volumes. When models included environmental risk factors as covariates, PRS-SCZ was only associated with lower SA/CV within the supramarginal cortex, superior temporal cortex and inferior frontal cortex. Moreover, no interactions were observed between PRS-SCZ and each of the environmental risk factors on brain structure. Overall, we identified brain structural correlates of PRS-SCZ predominantly within frontal and temporal regions. Some of these associations were independent of environmental risk factors, suggesting that they may represent biomarkers of genetic risk for schizophrenia.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ward, Dr Joey and Lyall, Dr Laura and Cullen, Dr Breda and Zhu, Miss Xingxing and Smith, Professor Daniel and Strawbridge, Dr Rona and Lyall, Dr Donald
• Authors: Zhu, X., Ward, J., Cullen, B., Lyall, D. M., Strawbridge, R. J., Smith, D. J., and Lyall, L. M.
• 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
• Journal Name: Schizophrenia Bulletin Open
• Publisher: Oxford University Press
• ISSN: 2632-7899
• ISSN (Online): 2632-7899
• Published Online: 24 September 2021
• Copyright Holders: Copyright © 2021 The Authors
• First Published: First published in Schizophrenia Bulletin Open 2(1):sgab042
• Publisher Policy: Reproduced under a Creative Commons licence

Related URLs

• Author

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302957		Mental Health Data Pathfinder	Daniel Smith	Medical Research Council (MRC)	MC_PC_17217	HW - Mental Health and Wellbeing