Blood-based epigenome-wide analyses of cognitive abilities

Daniel L McCartney; Robert F Hillary; Eleanor L S Conole; Daniel Trejo Banos; Danni A Gadd; Rosie M Walker; Cliff Nangle; Robin Flaig; Archie Campbell; Alison D Murray; Susana Muñoz Maniega; María Del C Valdés-Hernández; Mathew A Harris; Mark E Bastin; Joanna M Wardlaw; Sarah E Harris; David J Porteous; Elliot M Tucker-Drob; Andrew M McIntosh; Kathryn L Evans; Ian J Deary; Simon R Cox; Matthew R Robinson; Riccardo E Marioni

doi:10.1186/s13059-021-02596-5

Blood-based epigenome-wide analyses of cognitive abilities

Genome Biol. 2022 Jan 17;23(1):26. doi: 10.1186/s13059-021-02596-5.

Authors

Daniel L McCartney¹, Robert F Hillary², Eleanor L S Conole^{3

4}, Daniel Trejo Banos^{5

6}, Danni A Gadd², Rosie M Walker^{2

4}, Cliff Nangle², Robin Flaig², Archie Campbell², Alison D Murray⁷, Susana Muñoz Maniega^{3

4}, María Del C Valdés-Hernández^{3

4}, Mathew A Harris³, Mark E Bastin^{3

4}, Joanna M Wardlaw^{3

4}, Sarah E Harris³, David J Porteous², Elliot M Tucker-Drob^{8

9}, Andrew M McIntosh^{2

10}, Kathryn L Evans², Ian J Deary³, Simon R Cox¹¹, Matthew R Robinson¹², Riccardo E Marioni¹³

Affiliations

¹ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK. daniel.mccartney@ed.ac.uk.
² Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK.
³ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK.
⁴ Centre for Clinical Brain Sciences, UK Dementia Research Institute at the University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh BioQuarter, Edinburgh, EH16 4SB, UK.
⁵ Department of Quantitative Biomedicine, University of Zurich, Zurich, Switzerland.
⁶ Biomedical Informatics, University Hospital of Zurich, Zurich, Switzerland.
⁷ Aberdeen Biomedical Imaging Centre, University of Aberdeen, Aberdeen, Scotland, UK.
⁸ Department of Psychology, University of Texas, Austin, TX, USA.
⁹ Population Research Center and Center on Aging and Population Sciences, University of Texas, Austin, TX, USA.
¹⁰ Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
¹¹ Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. simon.cox@ed.ac.uk.
¹² Institute of Science and Technology Austria, 3400, Klosterneuburg, Austria. matthew.robinson@ist.ac.at.
¹³ Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, EH4 2XU, UK. riccardo.marioni@ed.ac.uk.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cognition
DNA Methylation
Epigenesis, Genetic*
Epigenome*
Genome-Wide Association Study / methods

Abstract

Publication types

MeSH terms

Grants and funding