title: Polygenic risk and white matter integrity in individuals at high risk of mood disorder.
abstract: BACKGROUND
  Bipolar disorder (BD) and major depressive disorder (MDD) are highly heritable and genetically overlapping conditions characterized by episodic elevation and/or depression of mood. Both demonstrate abnormalities in white matter integrity, measured with diffusion tensor magnetic resonance imaging, that are also heritable. However, it is unclear how these abnormalities relate to the underlying genetic architecture of each disorder. Genome-wide association studies have demonstrated a significant polygenic contribution to BD and MDD, where risk is attributed to the summation of many alleles of small effect. Determining the effects of an overall polygenic risk profile score on neuroimaging abnormalities might help to identify proxy measures of genetic susceptibility and thereby inform models of risk prediction.
  
  
  METHODS
  In the current study, we determined the extent to which common genetic variation underlying risk to mood disorders (BD and MDD) was related to fractional anisotropy, an index of white matter integrity. This was conducted in unaffected individuals at familial risk of mood disorder (n = 70) and comparison subjects (n = 62). Polygenic risk scores were calculated separately for BD and MDD on the basis of genome-wide association study data from the Psychiatric GWAS Consortia.
  
  
  RESULTS
  We report that a higher polygenic risk allele load for MDD was significantly associated with decreased white matter integrity across both groups in a large cluster, with a peak in the right-sided superior longitudinal fasciculus.
  
  
  CONCLUSIONS
  These findings suggest that the polygenic approach to examining brain imaging data might be a useful means of identifying traits linked to the genetic risk of mood disorders.
authors: Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. heather.whalley@ed.ac.uk
authors: Heather C
authors: HC
authors: Whalley
authors: Emma
authors: E
authors: Sprooten
authors: Suzanna
authors: S
authors: Hackett
authors: Lynsey
authors: L
authors: Hall
authors: Douglas H
authors: DH
authors: Blackwood
authors: David C
authors: DC
authors: Glahn
authors: Mark
authors: M
authors: Bastin
authors: Jeremy
authors: J
authors: Hall
authors: Stephen M
authors: SM
authors: Lawrie
authors: Jessika E
authors: JE
authors: Sussmann
authors: Andrew M
authors: AM
authors: McIntosh
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D003865:Major Depressive Disorder / Q000235:genetics / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance; D012307:Risk Factors; D055815:Young Adult
keywords: Bipolar disorder; diffusion tensor MRI; major depressive disorder; mood disorder; polygenic; white matter