title: 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.
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, United Kingdom.
authors.forename: L M
authors.initials: LM
authors.lastname: Reus
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, United Kingdom.
authors.forename: X
authors.initials: X
authors.lastname: Shen
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, United Kingdom.
authors.forename: J
authors.initials: J
authors.lastname: Gibson
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, United Kingdom.
authors.forename: E
authors.initials: E
authors.lastname: Wigmore
authors.affiliation: Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Ligthart
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, United Kingdom.
authors.forename: M J
authors.initials: MJ
authors.lastname: Adams
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
authors.forename: G
authors.initials: G
authors.lastname: Davies
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.|Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
authors.forename: S R
authors.initials: SR
authors.lastname: Cox
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, United Kingdom.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.|Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
authors.forename: S P
authors.initials: SP
authors.lastname: Hagenaars
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
authors.forename: M E
authors.initials: ME
authors.lastname: Bastin
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.|Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
authors.forename: I J
authors.initials: IJ
authors.lastname: Deary
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, United Kingdom.
authors.forename: H C
authors.initials: HC
authors.lastname: Whalley
authors.affiliation: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, EH10 5HF, United Kingdom.|Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, EH8 9JZ, United Kingdom.
authors.forename: A M
authors.initials: AM
authors.lastname: McIntosh
mesh_terms: D000328:Adult; D000368:Aged; D018070:Biological Specimen Banks; D001714:Bipolar Disorder / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008032:Limbic System / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D059906:Neuroimaging; D012306:Risk; D012559:Schizophrenia / Q000000981:diagnostic imaging* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D066127:White Matter / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology