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

Figures & data

Figure 1. Leukocyte DNA methylation in HLA-DRB5 and SLC24A4 in relation to dementia and Alzheimer’s disease. Volcano plots of beta values and significance level from logistic regression models of leukocyte DNA methylation M-values at in a) HLA-DRB5 and b) SLC24A4 in relation to dementia and Alzheimer’s disease (AD). Each point represent one individual CpG site. Models using the total sample were adjusted for age at blood sample, sex, and relatedness among twins. Co-twin control models were adjusted for age at blood sample.

Table 1. Gene-level significance of DNA methylation in leukocytes in relation to dementia and Alzheimer’s disease.

		Dementia		Alzheimer’s disease
	N CpG sites	Total sample	Co-twin control	Total sample	Co-twin control
BIN1	59	0.07	0.69	0.05	0.58
HLA-DRB5	12	0.02	<0.01	0.04	0.18
SORL1	47	0.06	0.75	0.10	0.96
SLC24A4	48	0.01	0.17	0.01	0.16
ABCA7	202	0.24	–	0.23	–

Number of CpG sites included and gene-level significance for each of the five genes. Logistic regression models were applied to test associations between CpG M-vaules and dementia or Alzheimer’s disease. Models using the total sample were adjusted for age at blood sample, sex, and relatedness among twins, and co-twin control models adjusted for age at blood sample. P-values for each CpG site across the genes were combined into a test statistic using the Fisher product method, and the statistical significance tested through random permutations. Bold numbers indicate significance at the α = 0.05 level. The co-twin control permutation test for ABCA7 did not converge.

Data availability statement

The SATSA data are available at National Archive of Computerized Data on Aging under accession number ICPSR 3843 (phenotypic data; https://www.icpsr.umich.edu/web/NACDA/studies/3843) and the EMBL‐EBI repository under accession number E‐MTAB‐7309 (DNA methylation data, 450K array; https://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-7309). Other data are held by the Swedish Twin Registry and can be applied for at https://ki.se/en/research/the-swedish-twin-registry.

All codes used to generate analysis data and for conducting analyses are available upon request to the corresponding author.