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

Sci Rep. 2017 Feb 10:7:42140. doi: 10.1038/srep42140.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biological Specimen Banks
  • Bipolar Disorder / diagnostic imaging*
  • Bipolar Disorder / genetics
  • Bipolar Disorder / metabolism
  • Bipolar Disorder / pathology
  • Brain Mapping
  • Cerebral Cortex / diagnostic imaging*
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Corpus Striatum / diagnostic imaging
  • Corpus Striatum / metabolism
  • Corpus Striatum / pathology
  • Depressive Disorder, Major / diagnostic imaging*
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / metabolism
  • Depressive Disorder, Major / pathology
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Limbic System / diagnostic imaging
  • Limbic System / metabolism
  • Limbic System / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Multifactorial Inheritance*
  • Neuroimaging
  • Risk
  • Schizophrenia / diagnostic imaging*
  • Schizophrenia / genetics
  • Schizophrenia / metabolism
  • Schizophrenia / pathology
  • White Matter / diagnostic imaging*
  • White Matter / metabolism
  • White Matter / pathology