@article{1131e6f293124d9fb1f4b96281fecaa7,
title = "General dimensions of human brain morphometry inferred from genome-wide association data",
abstract = "Understanding the neurodegenerative mechanisms underlying cognitive decline in the general population may facilitate early detection of adverse health outcomes in late life. This study investigates genetic links between brain morphometry, ageing and cognitive ability. We develop Genomic Principal Components Analysis (Genomic PCA) to model general dimensions of brain-wide morphometry at the level of their underlying genetic architecture. Genomic PCA is applied to genome-wide association data for 83 brain-wide volumes (36,778 UK Biobank participants) and we extract genomic principal components (PCs) to capture global dimensions of genetic covariance across brain regions (unlike ancestral PCs that index genetic similarity between participants). Using linkage disequilibrium score regression, we estimate genetic overlap between those general brain dimensions and cognitive ageing. The first genetic PCs underlying the morphometric organisation of 83 brain-wide regions accounted for substantial genetic variance (R2 = 40%) with the pattern of component loadings corresponding closely to those obtained from phenotypic analyses. Genetically more central regions to overall brain structure - specifically frontal and parietal volumes thought to be part of the central executive network - tended to be somewhat more susceptible towards age (r = −0.27). We demonstrate the moderate genetic overlap between the first PC underlying each of several structural brain networks and general cognitive ability (rg = 0.17–0.21), which was not specific to a particular subset of the canonical networks examined. We provide a multivariate framework integrating covariance across multiple brain regions and the genome, revealing moderate shared genetic etiology between brain-wide morphometry and cognitive ageing.",
keywords = "brain age, cognitive ability, complex traits, genetics, statistical modelling, structural brain networks, structural neuroimageing",
author = "F{\"u}rtjes, {Anna E.} and Ryan Arathimos and Coleman, {Jonathan R.I.} and Cole, {James H.} and Cox, {Simon R.} and Deary, {Ian J.} and {de la Fuente}, Javier and Madole, {James W.} and Tucker-Drob, {Elliot M.} and Ritchie, {Stuart J.}",
note = "Funding Information: Anna E. F{\"u}rtjes is funded by the Social, Genetic and Developmental Psychiatry Centre, King's College London and the National Institute of Health (NIH) grant R01AG054628. Stuart J. Ritchie is funded by the Jacobs Foundation. James H. Cole is funded by a UK Research & Innovation (UKRI) Innovation Fellowship (MR/R024790/1; MR/R024790/2). Javier de la Fuente is funded by the National Institutes of Health (NIH) grant R01AG054628. Javier de la Fuente and Elliot M. Tucker-Drob are members of the Population Research Center (PRC) and Center on Ageing and Population Sciences (CAPS) at The University of Texas at Austin, which are supported by NIH grants P2CHD042849 and P30AG066614. Javier de la Fuente, James W. Madole and Elliot M. Tucker-Drob were supported by NIH R01AG054628. Ian J. Deary is with the Lothian Birth Cohorts group, which is funded by Age UK (Disconnected Mind grant), the Medical Research Council (grant no. MR/R024065/1) and the University of Edinburgh's School of Philosophy, Psychology and Language Sciences. The contribution by Ryan Arathimos represents independent research part-funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The contribution by Jonathan R. I. Coleman represents independent research part-funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Simon R. Cox is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 221890/Z/20/Z). This research was funded in part by the Wellcome Trust [221890/Z/20/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The authors gratefully acknowledge the UK Biobank resource (https://www.ukbiobank.ac.uk/) and its research team, who have made this work possible (project number 18177). The authors acknowledge the use of the research computing facility at King's College London, Rosalind (https://rosalind.kcl.ac.uk), which is delivered in partnership with the National Institute for Health Research (NIHR) Biomedical Research Centres at South London & Maudsley and Guy's & St. Thomas{\textquoteright} NHS Foundation Trusts, and part-funded by capital equipment grants from the Maudsley Charity (award 980) and Guy's & St. Thomas{\textquoteright} Charity (TR130505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: Anna E. F{\"u}rtjes is funded by the Social, Genetic and Developmental Psychiatry Centre, King's College London and the National Institute of Health (NIH) grant R01AG054628. Stuart J. Ritchie is funded by the Jacobs Foundation. James H. Cole is funded by a UK Research & Innovation (UKRI) Innovation Fellowship (MR/R024790/1; MR/R024790/2). Javier de la Fuente is funded by the National Institutes of Health (NIH) grant R01AG054628. Javier de la Fuente and Elliot M. Tucker‐Drob are members of the Population Research Center (PRC) and Center on Ageing and Population Sciences (CAPS) at The University of Texas at Austin, which are supported by NIH grants P2CHD042849 and P30AG066614. Javier de la Fuente, James W. Madole and Elliot M. Tucker‐Drob were supported by NIH R01AG054628. Ian J. Deary is with the Lothian Birth Cohorts group, which is funded by Age UK (Disconnected Mind grant), the Medical Research Council (grant no. MR/R024065/1) and the University of Edinburgh's School of Philosophy, Psychology and Language Sciences. The contribution by Ryan Arathimos represents independent research part‐funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The contribution by Jonathan R. I. Coleman represents independent research part‐funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. Simon R. Cox is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (Grant Number 221890/Z/20/Z). This research was funded in part by the Wellcome Trust [221890/Z/20/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. The authors gratefully acknowledge the UK Biobank resource ( https://www.ukbiobank.ac.uk/ ) and its research team, who have made this work possible (project number 18177). The authors acknowledge the use of the research computing facility at King's College London, Rosalind ( https://rosalind.kcl.ac.uk ), which is delivered in partnership with the National Institute for Health Research (NIHR) Biomedical Research Centres at South London & Maudsley and Guy's & St. Thomas{\textquoteright} NHS Foundation Trusts, and part‐funded by capital equipment grants from the Maudsley Charity (award 980) and Guy's & St. Thomas{\textquoteright} Charity (TR130505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2023 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.",
year = "2023",
month = jun,
day = "1",
doi = "10.1002/hbm.26283",
language = "English",
journal = "Human Brain Mapping",
issn = "1065-9471",
publisher = "Wiley-Liss Inc.",
}