PT  - JOURNAL ARTICLE
AU  - Eleanor M. Wigmore
AU  - Toni-Kim Clarke
AU  - Mark J. Adams
AU  - Ana M. Fernandez-Pujals
AU  - Jude Gibson
AU  - David M. Howard
AU  - Gail Davies
AU  - Lynsey S. Hall
AU  - Yanni Zeng
AU  - Pippa A. Thomson
AU  - Caroline Hayward
AU  - Blair H. Smith
AU  - Lynne J. Hocking
AU  - Sandosh Padmanabhan
AU  - Ian J. Deary
AU  - David J. Porteous
AU  - Kristin K. Nicodemus
AU  - Andrew M. McIntosh
TI  - 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=5,766)
AID  - 10.1101/059352
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 059352
4099  - http://biorxiv.org/content/early/2016/12/08/059352.short
4100  - http://biorxiv.org/content/early/2016/12/08/059352.full
AB  - 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 ENIGMA consortium’s genome-wide association study (GWAS) of regional brain volume, we sought to test whether there is shared genetic architecture between 8 subcortical brain volumes and MDD. Using LD score regression utilising summary statistics from ENIGMA and the 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 other six brain regions studied were genetically correlated and amygdala volume heritability was too low for analysis. We also generated polygenic risk scores (PRS) to assess potential pleiotropy between regional brain volumes and MDD in three cohorts (Generation Scotland; Scottish Family Health Study (n=19,762), UK Biobank (n=24,048) and the English Longitudinal Study of Ageing (n=5,766). We used logistic regression to examine volumetric PRS and MDD and performed a meta-analysis across the three cohorts. No regional volumetric PRS demonstrated significant association with MDD or recurrent MDD. In this study we provide some evidence that hippocampal volume and MDD may share genetic architecture, albeit this did not survive multiple testing correction and was in the opposite direction to most reported phenotypic correlations. We therefore found no evidence to support a shared genetic architecture for MDD and regional subcortical volumes.