Leukocyte DNA methylation in Alzheimer´s disease associated genes: replication of findings from neuronal cells

Ida K Karlsson; Alexander Ploner; Yunzhang Wang; Margaret Gatz; Nancy L Pedersen; Sara Hägg

doi:10.1080/15592294.2022.2158285

Leukocyte DNA methylation in Alzheimer´s disease associated genes: replication of findings from neuronal cells

Epigenetics. 2023 Dec;18(1):2158285. doi: 10.1080/15592294.2022.2158285. Epub 2022 Dec 26.

Authors

Ida K Karlsson¹, Alexander Ploner¹, Yunzhang Wang¹, Margaret Gatz^{1

2}, Nancy L Pedersen^{1

3}, Sara Hägg¹

Affiliations

¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
² Center for Economic and Social Research, University of Southern California, Los Angeles, CA, USA.
³ Department of Psychology, University of Southern California, Los Angeles, CA, USA.

Abstract

Differences in gene-wide DNA methylation of the Alzheimer's disease (AD)-associated genes BIN1, HLA-DRB5, SORL1, SLC24A4, and ABCA7 are reported to be associated with AD in post-mortem brain samples. We investigated whether the same associations could be found in leukocytes collected pre-mortem. Using cohort data of 544 Swedish twins (204 dementia diagnoses), we replicated the findings in HLA-DRB5 and SLC24A4 at P < 0.05. However, co-twin control analyses indicated that the associations were partly explained by familial confounding. Thus, DNA methylation differences in HLA-DRB5 and SLC24A4 are present in both neuronal cells and leukocytes, and not fully explained familial factors.

Keywords: Alzheimer’s disease; DNA methylation; Dementia; twins.

Publication types

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

MeSH terms

Alzheimer Disease* / genetics
Brain
DNA Methylation
HLA-DRB5 Chains / genetics
Humans
LDL-Receptor Related Proteins / genetics
Membrane Transport Proteins / genetics

Substances

HLA-DRB5 Chains
SORL1 protein, human
LDL-Receptor Related Proteins
Membrane Transport Proteins

Grants and funding

This work was supported by the National Institutes of Health; The Strategic Research Program in Epidemiology at Karolinska Institutet; King Gustaf V and Queen Victoria’s Foundation of Freemasons; Vetenskapsrådet; Vetenskapsrådet; Vetenskapsrådet.