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

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.

Polygenic Risk Scores in Clinical Psychology: Bridging Genomic Risk to Individual Differences

“…Cognitive function in older adults (Liebers et al, 2016) White matter integrity (Alloza et al, 2017) 28 SCZ, 36 CON SCZ diagnosis: 0.057; NS associations with network. Gray matter volume and white matter integrity (Reus et al, 2017) Volume: 978 WM: 816 NS.…”

The endocytic membrane trafficking pathway plays a major role in the risk of Parkinson's disease

“…PRS has emerged as a probabilistic tool to infer how independent loci with small effects can be collapsed into a single numerical value useful in predicting the risk of a disease. It has been successfully used to dissect the genetic complexity of brain disorder and quantify risk in many common complex conditions for early detection, prevention and therapeutics . Here, we assessed the overall cumulative contribution of EMTP‐specific loci/genes in PD risk through PRS calculations.…”

Schizophrenia-associated genomic copy number variants and subcortical brain volumes in the UK Biobank

“…In summary, previous unsuccessful attempts to associate common genetic risk with subcortical brain volumes 11,38 resulted in the hypothesis that these biomarkers could not associate with genetic risk for SZ. Here we prove that genetic risk factors associated with SZ, at least from the risk conferred by In all the cases, results after controlling for the effects of age, sex and brain size.…”