No association of the variant rs11887120 in DNMT3A with cognitive decline in individuals with mild cognitive impairment

Katharina Bey; Steffen Wolfsgruber; Ilker Karaca; Holger Wagner; Roy Lardenoije; Julian Becker; Esther Milz; Johannes Kornhuber; Oliver Peters; Lutz Frölich; Michael Hüll; Eckart Rüther; Jens Wiltfang; Steffi Riedel-Heller; Martin Scherer; Frank Jessen; Wolfgang Maier; Daniel L van den Hove; Bart Pf Rutten; Michael Wagner; Alfredo Ramirez

doi:10.2217/epi-2015-0014

No association of the variant rs11887120 in DNMT3A with cognitive decline in individuals with mild cognitive impairment

Epigenomics. 2016 May;8(5):593-8. doi: 10.2217/epi-2015-0014. Epub 2016 Apr 19.

Authors

Katharina Bey¹, Steffen Wolfsgruber^{1

2}, Ilker Karaca¹, Holger Wagner¹, Roy Lardenoije³, Julian Becker¹, Esther Milz⁴, Johannes Kornhuber⁵, Oliver Peters⁶, Lutz Frölich⁷, Michael Hüll⁸, Eckart Rüther⁹, Jens Wiltfang⁹, Steffi Riedel-Heller¹⁰, Martin Scherer¹¹, Frank Jessen^{1

2

4}, Wolfgang Maier^{1

2}, Daniel L van den Hove^{3

12}, Bart Pf Rutten³, Michael Wagner^{1

2}, Alfredo Ramirez^{1

13}

Affiliations

¹ Department of Psychiatry & Psychotherapy, University of Bonn, 53127 Bonn, Germany.
² German Center for Neurodegenerative Diseases (DZNE), 53175 Bonn, Germany.
³ Department of Psychiatry & Neuropsychology, School for Mental Health & Neuroscience, European Graduate School of Neuroscience (EURON), Maastricht University, 6229 ER Maastricht, The Netherlands.
⁴ Department of Psychiatry & Psychotherapy, University of Cologne, 50937 Cologne, Germany.
⁵ Department of Psychiatry & Psychotherapy, Universitätsklinikum Erlangen, & Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany.
⁶ Department of Psychiatry, Charité, 14050 Berlin, Germany.
⁷ Department of Geriatric Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, 68159 Mannheim, Germany.
⁸ Centre for Geriatric Medicine & Section of Gerontopsychiatry & Neuropsychology, Medical School, University of Freiburg, 79106 Freiburg, Germany.
⁹ Department of Psychiatry & Psychotherapy, University of Göttingen, 37075 Göttingen, Germany.
¹⁰ Institute of Social Medicine, Occupational Health & Public Health, University of Leipzig, 04103 Leipzig, Germany.
¹¹ Department of Primary Medical Care, University Medical Centre Hamburg-Eppendorf, 20246 Hamburg, Germany.
¹² Laboratory of Translational Neuroscience, Department of Psychiatry, Psychosomatics & Psychotherapy, University of Würzburg, 97080 Würzburg, Germany.
¹³ Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany.

PMID: 27092400
DOI: 10.2217/epi-2015-0014

Abstract

Alterations in DNA methylation have been associated with cognitive decline and Alzheimer's disease. A recent study of mild cognitive impairment (MCI) reported a significant association between annual decline in cognitive function and the rs11887120 SNP located in DNMT3A, a gene implicated in DNA methylation. Here, we aimed to replicate this finding in two independent MCI cohorts (n = 1024); however, no significant association was observed in either cohort or the pooled dataset. In stratified analyses for conversion to Alzheimer's disease status, no association between rs11887120 and cognitive decline was observed in either converters or nonconverters. In conclusion, our analyses provide no support for the hypothesis that genetic variants in DNMT3A are implicated in cognitive performance decline in individuals with MCI.

Keywords: Alzheimer's disease; DNA methylation; DNA methyltransferase 3a; DNMT3A; MCI; aging; cognitive decline; epigenetics; mild cognitive impairment; rs11887120.

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease / genetics*
Alzheimer Disease / psychology
Case-Control Studies
Cognition
Cognitive Dysfunction / genetics*
Cognitive Dysfunction / psychology
DNA (Cytosine-5-)-Methyltransferases / genetics*
DNA Methyltransferase 3A
Disease Progression
Female
Gene Frequency
Genetic Association Studies
Humans
Male
Polymorphism, Single Nucleotide

Substances

DNMT3A protein, human
DNA (Cytosine-5-)-Methyltransferases
DNA Methyltransferase 3A