Association of polygenic risk for major psychiatric illness with subcortical volumes and white matter integrity in UK Biobank

L. M. Reus, X. Shen, J. Gibson, E. Wigmore, L. Ligthart, M. J. Adams, G. Davies, S. R. Cox, S. P. Hagenaars, M. E. Bastin, I. J. Deary, H. C. Whalley*, A. M. McIntosh

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Major depressive disorder (MDD), schizophrenia (SCZ) and bipolar disorder (BP) are common, disabling and heritable psychiatric diseases with a complex overlapping polygenic architecture. Individuals with these disorders, as well as their unaffected relatives, show widespread structural differences in corticostriatal and limbic networks. Structural variation in many of these brain regions is also heritable and polygenic but whether their genetic architecture overlaps with that of major psychiatric disorders is unknown. We sought to address this issue by examining the impact of polygenic risk of MDD, SCZ, and BP on subcortical brain volumes and white matter (WM) microstructure in a large single sample of neuroimaging data; the UK Biobank Imaging study. The first release of UK Biobank imaging data comprised participants with overlapping genetic data and subcortical volumes (N = 978) and WM measures (N = 816). The calculation of polygenic risk scores was based on genome-wide association study results generated by the Psychiatric Genomics Consortium. Our findings indicated no statistically significant associations between either subcortical volumes or WM microstructure, and polygenic risk for MDD, SCZ or BP. These findings suggest that subcortical brain volumes and WM microstructure may not be closely linked to the genetic mechanisms of major psychiatric disorders.

Original languageEnglish
Article number42140
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 10 Feb 2017

Funding

This work was supported by a grant of the Wellcome Trust Strategic Award "Stratifying Resilience and Depression Longitudinally" (STRADL) (reference 104036/Z/14/Z). We thank the UK Biobank participants for their participation, and the UK Biobank team for their work in collecting and providing these data for analysis. Part of the work was undertaken in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1); funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. Age UK (The Disconnected Mind project) also provided support for the work undertaken at CCACE. LMR was supported by an Erasmus Traineeship Grant. XS receives support from China Scholarship Council. HCW is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. SRC was supported by MRC grant MR/M013111/1. IJD is supported by the Medical Research Council award to CCACE (MR/K026992/1) and by the Dementias Platform UK (MR/L015382/1). IJD and SRC are additionally supported by the Age UKfunded Disconnected Mind project (http://www.disconnectedmind.ed.ac.uk). A.M.M. has previously received grant support from Pfizer, Lilly and Janssen.

FundersFunder number
Dementias Platform UKMR/L015382/1
JMAS
Lilly and Janssen
University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology
cross council Lifelong Health and Wellbeing Initiative
Pfizer
Wellcome Trust104036/Z/14/Z
Royal College of Physicians of Edinburgh
Medical Research CouncilMR/K026992/1, MC_qA137853, MR/M013111/1
Biotechnology and Biological Sciences Research Council
University of Edinburgh
China Scholarship Council
Centre for Cognitive Ageing and Cognitive Epidemiology

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