The influence of polygenic risk for bipolar disorder on neural activation assessed using fMRI

H. C. Whalley, M. Papmeyer, E. Sprooten, L. Romaniuk, D. H. Blackwood, D. C. Glahn, J. Hall, S. M. Lawrie, J. E. Sussmann, A. M. McIntosh

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Genome-wide association studies (GWAS) have demonstrated a significant polygenic contribution to bipolar disorder (BD) where disease risk is determined by the summation of many alleles of small individual magnitude. Modelling polygenic risk scores may be a powerful way of identifying disrupted brain regions whose genetic architecture is related to that of BD. We determined the extent to which common genetic variation underlying risk to BD affected neural activation during an executive processing/language task in individuals at familial risk of BD and healthy controls. Polygenic risk scores were calculated for each individual based on GWAS data from the Psychiatric GWAS Consortium Bipolar Disorder Working Group (PGC-BD) of over 16 000 subjects. The familial group had a significantly higher polygene score than the control group (P=0.04). There were no significant group by polygene interaction effects in terms of association with brain activation. However, we did find that an increasing polygenic risk allele load for BD was associated with increased activation in limbic regions previously implicated in BD, including the anterior cingulate cortex and amygdala, across both groups. The findings suggest that this novel polygenic approach to examine brain-imaging data may be a useful means of identifying genetically mediated traits mechanistically linked to the aetiology of BD.

Original languageEnglish (US)
Pages (from-to)e130
JournalTranslational psychiatry
Volume2
DOIs
StatePublished - 2012
Externally publishedYes

Keywords

  • amygdala
  • anterior cingulate
  • bipolar disorder
  • fMRI
  • polygenic

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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    Whalley, H. C., Papmeyer, M., Sprooten, E., Romaniuk, L., Blackwood, D. H., Glahn, D. C., Hall, J., Lawrie, S. M., Sussmann, J. E., & McIntosh, A. M. (2012). The influence of polygenic risk for bipolar disorder on neural activation assessed using fMRI. Translational psychiatry, 2, e130. https://doi.org/10.1038/tp.2012.60