King's College London

Research portal

Impact of Polygenic Risk for Schizophrenia on Cortical Structure in UK Biobank

Research output: Contribution to journalArticlepeer-review

Emma Neilson, Xueyi Shen, Simon R Cox, Toni-Kim Clarke, Eleanor M Wigmore, Jude Gibson, David M Howard, Mark J Adams, Mat A Harris, Gail Davies, Ian J Deary, Heather C Whalley, Andrew M McIntosh, Stephen M Lawrie

Original languageEnglish
Pages (from-to)536-544
Number of pages9
JournalBiological psychiatry
Issue number7
Early online date22 Apr 2019
Accepted/In press5 Apr 2019
E-pub ahead of print22 Apr 2019
Published1 Oct 2019

Bibliographical note

Copyright © 2019. Published by Elsevier Inc.


King's Authors


BACKGROUND: Schizophrenia is a neurodevelopmental disorder with many genetic variants of individually small effect contributing to phenotypic variation. Lower cortical thickness (CT), surface area, and cortical volume have been demonstrated in people with schizophrenia. Furthermore, a range of obstetric complications (e.g., lower birth weight) are consistently associated with an increased risk for schizophrenia. We investigated whether a high polygenic risk score for schizophrenia (PGRS-SCZ) is associated with CT, surface area, and cortical volume in UK Biobank, a population-based sample, and tested for interactions with birth weight.

METHODS: Data were available for 2864 participants (nmale/nfemale = 1382/1482; mean age = 62.35 years, SD = 7.40). Linear mixed models were used to test for associations among PGRS-SCZ and cortical volume, surface area, and CT and between PGRS-SCZ and birth weight. Interaction effects of these variables on cortical structure were also tested.

RESULTS: We found a significant negative association between PGRS-SCZ and global CT; a higher PGRS-SCZ was associated with lower CT across the whole brain. We also report a significant negative association between PGRS-SCZ and insular lobe CT. PGRS-SCZ was not associated with birth weight and no PGRS-SCZ × birth weight interactions were found.

CONCLUSIONS: These results suggest that individual differences in CT are partly influenced by genetic variants and are most likely not due to factors downstream of disease onset. This approach may help to elucidate the genetic pathophysiology of schizophrenia. Further investigation in case-control and high-risk samples could help identify any localized effects of PGRS-SCZ, and other potential schizophrenia risk factors, on CT as symptoms develop.

Download statistics

No data available

View graph of relations

© 2020 King's College London | Strand | London WC2R 2LS | England | United Kingdom | Tel +44 (0)20 7836 5454