@article{1a6e6046e9ad437a9a72666a1707c17e,
title = "Blood-based epigenome-wide analyses of cognitive abilities",
abstract = "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.",
keywords = "Cognitive ability, DNA methylation, EWAS, Epidemiology, Prediction",
author = "Mccartney, {Daniel L.} and Hillary, {Robert F.} and Conole, {Eleanor L. S.} and Banos, {Daniel Trejo} and Gadd, {Danni A.} and Walker, {Rosie M.} and Cliff Nangle and Robin Flaig and Archie Campbell and Murray, {Alison D.} and Maniega, {Susana Mu{\~n}oz} and Vald{\'e}s-hern{\'a}ndez, {Mar{\'i}a Del C.} and Harris, {Mathew A.} and Bastin, {Mark E.} and Wardlaw, {Joanna M.} and Harris, {Sarah E.} and Porteous, {David J.} and Tucker-drob, {Elliot M.} and Mcintosh, {Andrew M.} and Evans, {Kathryn L.} and Deary, {Ian J.} and Cox, {Simon R.} and Robinson, {Matthew R.} and Marioni, {Riccardo E.}",
note = "Funding Information: 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. Funding Information: 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{\textquoteright}s Society major project grant AS-PG-19b-010. Funding Information: R.E.M has received a speaker fee from Illumina and is an advisor to the Epigenetic Clock Development Foundation. A.M.M has previously received speaker fees from Janssen and Illumina and research funding from The Sackler Trust. All other authors declare no competing interests. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = jan,
day = "17",
doi = "10.1186/s13059-021-02596-5",
language = "English",
volume = "23",
journal = "Genome Biology",
issn = "1465-6906",
publisher = "BioMed Central",
number = "1",
}