title: Structural Brain MRI Trait Polygenic Score Prediction of Cognitive Abilities.
abstract: Structural brain magnetic resonance imaging (MRI) traits share part of their genetic variance with cognitive traits. Here, we use genetic association results from large meta-analytic studies of genome-wide association (GWA) for brain infarcts (BI), white matter hyperintensities, intracranial, hippocampal, and total brain volumes to estimate polygenic scores for these traits in three Scottish samples: Generation Scotland: Scottish Family Health Study (GS:SFHS), and the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921). These five brain MRI trait polygenic scores were then used to: (1) predict corresponding MRI traits in the LBC1936 (numbers ranged 573 to 630 across traits), and (2) predict cognitive traits in all three cohorts (in 8,115-8,250 persons). In the LBC1936, all MRI phenotypic traits were correlated with at least one cognitive measure, and polygenic prediction of MRI traits was observed for intracranial volume. Meta-analysis of the correlations between MRI polygenic scores and cognitive traits revealed a significant negative correlation (maximal r = 0.08) between the HV polygenic score and measures of global cognitive ability collected in childhood and in old age in the Lothian Birth Cohorts. The lack of association to a related general cognitive measure when including the GS:SFHS points to either type 1 error or the importance of using prediction samples that closely match the demographics of the GWA samples from which prediction is based. Ideally, these analyses should be repeated in larger samples with data on both MRI and cognition, and using MRI GWA results from even larger meta-analysis studies.
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: Michelle
authors.initials: M
authors.lastname: Luciano
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: Riccardo E
authors.initials: RE
authors.lastname: Marioni
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Valdés Hernández
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: Susana
authors.initials: S
authors.lastname: Muñoz Maniega
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: Iona F
authors.initials: IF
authors.lastname: Hamilton
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Royle
authors.affiliation: Inserm Research Center for Epidemiology and Biostatistics (U897)-Team Neuroepidemiology,Bordeaux,France.
authors.forename: Ganesh
authors.initials: G
authors.lastname: Chauhan
authors.affiliation: Cardiovascular Health Research Unit,University of Washington,Seattle,Washington,USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.affiliation: Inserm Research Center for Epidemiology and Biostatistics (U897)-Team Neuroepidemiology,Bordeaux,France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Debette
authors.affiliation: Department of Neurology and Center for Neuroscience,University of California at Davis,Davis,California,USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Brown Foundation Institute of Molecular Medicine,Division of Epidemiology,School of Public Health,University of Texas Health Science Center at Houston,Houston,Texas,USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.affiliation: Department of Neurology,Medical University Graz,Graz,Austria.
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Departments of Epidemiology,Radiology and Neurology at Erasmus MC University Medical Center,Rotterdam,the Netherlands.
authors.forename: M Arfan
authors.initials: MA
authors.lastname: Ikram
authors.affiliation: Laboratory of Epidemiology,Demography,and Biometry,National Institute on Aging,Bethesda,Maryland,USA.
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.affiliation: Department of Neurology,Boston University School of Medicine,Boston,Massachusetts,USA.
authors.forename: Sudha
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Bastin
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wardlaw
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology,University of Edinburgh,Edinburgh,UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Deary
mesh_terms: D001921:Brain / Q000033:anatomy & histology* / Q000502:physiology*; D003071:Cognition; D005260:Female; D005544:Forecasting; D055106:Genome-Wide Association Study; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D009483:Neuropsychological Tests
keywords: brain infarct; general cognitive ability; hippocampal volume; intracranial volume; polygenic prediction; total brain volume; white matter hyperintensities