title: Blood DNA methylation age is not associated with cognitive functioning in middle-aged monozygotic twins.
abstract: The epigenetic clock, also known as DNA methylation age (DNAmAge), represents age-related changes of DNA methylation at multiple sites of the genome and is suggested to be a biomarker for biological age. Elevated blood DNAmAge is associated with all-cause mortality, with the strongest effects reported in a recent intrapair twin study where epigenetically older twins had increased mortality risk in comparison to their co-twins. In the study presented here, we hypothesize that DNAmAge in blood is associated with cross-sectional and longitudinal cognitive abilities in middle-aged individuals. In 486 monozygotic twins, we investigated the association of DNAmAge, difference between DNAmAge and chronological age and age acceleration with cognition. Despite using a powerful paired twin design, we found no evidence for association of blood DNAmAge with cognitive abilities. This observation was confirmed in unpaired analyses, where DNAmAge initially correlated with cognitive abilities, until adjusting for chronological age. Overall, our study shows that for middle-aged individuals DNAmAge calculated in blood does not correlate with cognitive abilities.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark. Electronic address: as@biomed.au.dk.
authors.forename: A
authors.initials: A
authors.lastname: Starnawska
authors.affiliation: The Danish Aging Research Center, and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark; Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: Q
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Max Planck Odense Center on the Biodemography of Aging, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: A
authors.initials: A
authors.lastname: Lenart
authors.affiliation: The Danish Aging Research Center, and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark; Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: M
authors.initials: M
authors.lastname: McGue
authors.affiliation: The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Mors
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
authors.forename: A D
authors.initials: AD
authors.lastname: Børglum
authors.affiliation: The Danish Aging Research Center, and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark; Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Christensen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark; Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Nyegaard
authors.affiliation: The Danish Aging Research Center, and The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Christiansen
mesh_terms: D000375:Aging / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D003430:Cross-Sectional Studies; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D014430:Twins, Monozygotic
keywords: Cognition; Cross-sectional; DNA methylation; Epigenetic clock; Longitudinal; Monozygotic twins; Whole blood