Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland (n=19 762), UK Biobank (n=24 048) and the English Longitudinal Study of Ageing (n=5766)

Wigmore, E. M. et al. (2017) Do regional brain volumes and major depressive disorder share genetic architecture? A study of Generation Scotland (n=19 762), UK Biobank (n=24 048) and the English Longitudinal Study of Ageing (n=5766). Translational Psychiatry, 7(8), e1205. (doi: 10.1038/tp.2017.148) (PMID:28809859)

[img]
Preview
Text
146674.pdf - Published Version
Available under License Creative Commons Attribution.

414kB

Abstract

Major depressive disorder (MDD) is a heritable and highly debilitating condition. It is commonly associated with subcortical volumetric abnormalities, the most replicated of these being reduced hippocampal volume. Using the most recent published data from Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium's genome-wide association study of regional brain volume, we sought to test whether there is shared genetic architecture between seven subcortical brain volumes and intracranial volume (ICV) and MDD. We explored this using linkage disequilibrium score regression, polygenic risk scoring (PRS) techniques, Mendelian randomisation (MR) analysis and BUHMBOX. Utilising summary statistics from ENIGMA and Psychiatric Genomics Consortium, we demonstrated that hippocampal volume was positively genetically correlated with MDD (rG=0.46, P=0.02), although this did not survive multiple comparison testing. None of the other six brain regions studied were genetically correlated and amygdala volume heritability was too low for analysis. Using PRS analysis, no regional volumetric PRS demonstrated a significant association with MDD or recurrent MDD. MR analysis in hippocampal volume and MDD identified no causal association, however, BUHMBOX analysis identified genetic subgrouping in GS:SFHS MDD cases only (P=0.00281). In this study, we provide some evidence that hippocampal volume and MDD may share genetic architecture in a subgroup of individuals, albeit the genetic correlation did not survive multiple testing correction and genetic subgroup heterogeneity was not replicated. In contrast, we found no evidence to support a shared genetic architecture between MDD and other regional subcortical volumes or ICV.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Padmanabhan, Professor Sandosh
Authors: Wigmore, E. M., Clarke, T.-K., Howard, D. M., Adams, M. J., Hall, L. S., Zeng, Y., Gibson, J., Davies, G., Fernandez-Pujals, A. M., Thomson, P. A., Hayward, C., Smith, B. H., Hocking, L. J., Padmanabhan, S., Deary, I. J., Porteous, D. J., Nicodemus, K. K., and McIntosh, A. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Translational Psychiatry
Publisher:Nature Publishing Group
ISSN:2158-3188
ISSN (Online):2158-3188
Published Online:15 August 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Translational Psychiatry 7(8): e1205
Publisher Policy:Reproduced under a Creative Commons license

University Staff: Request a correction | Enlighten Editors: Update this record

Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
381721Generation ScotlandAnna DominiczakChief Scientist office (CSO)CZD/16/6RI CARDIOVASCULAR & MEDICAL SCIENCES