---
_id: '10702'
abstract:
- lang: eng
  text: 'Background: Blood-based markers of cognitive functioning might provide an
    accessible way to track neurodegeneration years prior to clinical manifestation
    of cognitive impairment and dementia. Results: Using blood-based epigenome-wide
    analyses of general cognitive function, we show that individual differences in
    DNA methylation (DNAm) explain 35.0% of the variance in general cognitive function
    (g). A DNAm predictor explains ~4% of the variance, independently of a polygenic
    score, in two external cohorts. It also associates with circulating levels of
    neurology- and inflammation-related proteins, global brain imaging metrics, and
    regional cortical volumes. Conclusions: As sample sizes increase, the ability
    to assess cognitive function from DNAm data may be informative in settings where
    cognitive testing is unreliable or unavailable.'
acknowledgement: 'GS received core support from the Chief Scientist Office of the
  Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council
  (HR03006). Genotyping and DNA methylation profiling of the GS samples was carried
  out by the Genetics Core Laboratory at the Edinburgh Clinical Research Facility,
  Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome
  Trust (Wellcome Trust Strategic Award STratifying Resilience and Depression Longitudinally
  (STRADL; Reference 104036/Z/14/Z). The DNA methylation data assayed for Generation
  Scotland was partially funded by a 2018 NARSAD Young Investigator Grant from the
  Brain & Behavior Research Foundation (Ref: 27404; awardee: Dr David M Howard) and
  by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh (Awardee:
  Dr Heather C Whalley). LBC1936 MRI brain imaging was supported by Medical Research
  Council (MRC) grants [G0701120], [G1001245], [MR/M013111/1] and [MR/R024065/1].
  Magnetic resonance image acquisition and analyses were conducted at the Brain Research
  Imaging Centre, Neuroimaging Sciences, University of Edinburgh (www.bric.ed.ac.uk)
  which is part of SINAPSE (Scottish Imaging Network: A Platform for Scientific Excellence)
  collaboration (www.sinapse.ac.uk) funded by the Scottish Funding Council and the
  Chief Scientist Office. This work was supported by the European Union Horizon 2020
  (PHC.03.15, project No 666881), SVDs@Target, the Fondation Leducq Transatlantic
  Network of Excellence for the Study of Perivascular Spaces in Small Vessel Disease
  [ref no. 16 CVD 05]. We thank the LBC1936 participants and team members who contributed
  to these studies. The LBC1936 is supported by Age UK (Disconnected Mind project,
  which supports S.E.H.), the Medical Research Council (G0701120, G1001245, MR/M013111/1,
  MR/R024065/1) and the University of Edinburgh. Methylation typing of LBC1936 was
  supported by the Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund
  award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University
  of Edinburgh, and The University of Queensland. Genotyping was funded by the Biotechnology
  and Biological Sciences Research Council (BB/F019394/1). Proteomic analyses in LBC1936
  were supported by the Age UK grant and NIH Grants R01AG054628 and R01AG05462802S1.
  M.V.H. is funded by the Row Fogo Charitable Trust (Grant no. BROD.FID3668413). J.M.W
  is supported by the UK Dementia Research Institute which receives its funding from
  DRI Ltd, funded by the UK Medical Research Council, Alzheimers Society and Alzheimers
  Research UK. R.F.H., E.L.S.C and D.A.G. are supported by funding from the Wellcome
  Trust 4 year PhD in Translational Neuroscience: training the next generation of
  basic neuroscientists to embrace clinical research [108890/Z/15/Z]. E.M.T.D. was
  supported by the National Institutes of Health (NIH) grants R01AG054628, R01MH120219,
  R01HD083613, P2CHD042849 and P30AG066614. S.R.C. was also supported by a National
  Institutes of Health (NIH) research grant R01AG054628 and is supported by a Sir
  Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society
  (Grant Number 221890/Z/20/Z). D.L.Mc.C. and R.E.M. are supported by Alzheimers Research
  UK major project grant ARUK/PG2017B/10. R.E.M. is supported by Alzheimer’s Society
  major project grant AS-PG-19b-010. This research was funded in whole, or in part,
  by Wellcome [104036/Z/14/Z and 108890/Z/15/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.'
article_number: '26'
article_processing_charge: No
article_type: original
author:
- first_name: Daniel L.
  full_name: McCartney, Daniel L.
  last_name: McCartney
- first_name: Robert F.
  full_name: Hillary, Robert F.
  last_name: Hillary
- first_name: Eleanor L.S.
  full_name: Conole, Eleanor L.S.
  last_name: Conole
- first_name: Daniel Trejo
  full_name: Banos, Daniel Trejo
  last_name: Banos
- first_name: Danni A.
  full_name: Gadd, Danni A.
  last_name: Gadd
- first_name: Rosie M.
  full_name: Walker, Rosie M.
  last_name: Walker
- first_name: Cliff
  full_name: Nangle, Cliff
  last_name: Nangle
- first_name: Robin
  full_name: Flaig, Robin
  last_name: Flaig
- first_name: Archie
  full_name: Campbell, Archie
  last_name: Campbell
- first_name: Alison D.
  full_name: Murray, Alison D.
  last_name: Murray
- first_name: Susana Muñoz
  full_name: Maniega, Susana Muñoz
  last_name: Maniega
- first_name: María Del C.
  full_name: Valdés-Hernández, María Del C.
  last_name: Valdés-Hernández
- first_name: Mathew A.
  full_name: Harris, Mathew A.
  last_name: Harris
- first_name: Mark E.
  full_name: Bastin, Mark E.
  last_name: Bastin
- first_name: Joanna M.
  full_name: Wardlaw, Joanna M.
  last_name: Wardlaw
- first_name: Sarah E.
  full_name: Harris, Sarah E.
  last_name: Harris
- first_name: David J.
  full_name: Porteous, David J.
  last_name: Porteous
- first_name: Elliot M.
  full_name: Tucker-Drob, Elliot M.
  last_name: Tucker-Drob
- first_name: Andrew M.
  full_name: McIntosh, Andrew M.
  last_name: McIntosh
- first_name: Kathryn L.
  full_name: Evans, Kathryn L.
  last_name: Evans
- first_name: Ian J.
  full_name: Deary, Ian J.
  last_name: Deary
- first_name: Simon R.
  full_name: Cox, Simon R.
  last_name: Cox
- first_name: Matthew Richard
  full_name: Robinson, Matthew Richard
  id: E5D42276-F5DA-11E9-8E24-6303E6697425
  last_name: Robinson
  orcid: 0000-0001-8982-8813
- first_name: Riccardo E.
  full_name: Marioni, Riccardo E.
  last_name: Marioni
citation:
  ama: McCartney DL, Hillary RF, Conole ELS, et al. Blood-based epigenome-wide analyses
    of cognitive abilities. <i>Genome Biology</i>. 2022;23(1). doi:<a href="https://doi.org/10.1186/s13059-021-02596-5">10.1186/s13059-021-02596-5</a>
  apa: McCartney, D. L., Hillary, R. F., Conole, E. L. S., Banos, D. T., Gadd, D.
    A., Walker, R. M., … Marioni, R. E. (2022). Blood-based epigenome-wide analyses
    of cognitive abilities. <i>Genome Biology</i>. Springer Nature. <a href="https://doi.org/10.1186/s13059-021-02596-5">https://doi.org/10.1186/s13059-021-02596-5</a>
  chicago: McCartney, Daniel L., Robert F. Hillary, Eleanor L.S. Conole, Daniel Trejo
    Banos, Danni A. Gadd, Rosie M. Walker, Cliff Nangle, et al. “Blood-Based Epigenome-Wide
    Analyses of Cognitive Abilities.” <i>Genome Biology</i>. Springer Nature, 2022.
    <a href="https://doi.org/10.1186/s13059-021-02596-5">https://doi.org/10.1186/s13059-021-02596-5</a>.
  ieee: D. L. McCartney <i>et al.</i>, “Blood-based epigenome-wide analyses of cognitive
    abilities,” <i>Genome Biology</i>, vol. 23, no. 1. Springer Nature, 2022.
  ista: McCartney DL, Hillary RF, Conole ELS, Banos DT, Gadd DA, Walker RM, Nangle
    C, Flaig R, Campbell A, Murray AD, Maniega SM, Valdés-Hernández MDC, Harris MA,
    Bastin ME, Wardlaw JM, Harris SE, Porteous DJ, Tucker-Drob EM, McIntosh AM, Evans
    KL, Deary IJ, Cox SR, Robinson MR, Marioni RE. 2022. Blood-based epigenome-wide
    analyses of cognitive abilities. Genome Biology. 23(1), 26.
  mla: McCartney, Daniel L., et al. “Blood-Based Epigenome-Wide Analyses of Cognitive
    Abilities.” <i>Genome Biology</i>, vol. 23, no. 1, 26, Springer Nature, 2022,
    doi:<a href="https://doi.org/10.1186/s13059-021-02596-5">10.1186/s13059-021-02596-5</a>.
  short: D.L. McCartney, R.F. Hillary, E.L.S. Conole, D.T. Banos, D.A. Gadd, R.M.
    Walker, C. Nangle, R. Flaig, A. Campbell, A.D. Murray, S.M. Maniega, M.D.C. Valdés-Hernández,
    M.A. Harris, M.E. Bastin, J.M. Wardlaw, S.E. Harris, D.J. Porteous, E.M. Tucker-Drob,
    A.M. McIntosh, K.L. Evans, I.J. Deary, S.R. Cox, M.R. Robinson, R.E. Marioni,
    Genome Biology 23 (2022).
date_created: 2022-01-30T23:01:33Z
date_published: 2022-01-17T00:00:00Z
date_updated: 2023-08-02T14:05:13Z
day: '17'
ddc:
- '570'
department:
- _id: MaRo
doi: 10.1186/s13059-021-02596-5
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project:
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  grant_number: PCEGP3_181181
  name: Improving estimation and prediction of common complex disease risk
publication: Genome Biology
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title: Blood-based epigenome-wide analyses of cognitive abilities
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...