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)

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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
Glasgow Author(s) Enlighten ID:Ward, Dr Joey and Lyall, Dr Laura and Zhu, Xingxing and Cullen, Dr Breda 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 > 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:Schizophrenia Bulletin Open
Publisher:Oxford University Press
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
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
302957Mental Health Data PathfinderDaniel SmithMedical Research Council (MRC)MC_PC_17217HW - Mental Health and Wellbeing