Fig. 3

The DNA methylation status of the ADARB2 gene is associated with Alzheimer’s disease. The DNA methylation level of region chr10:1,405,405-366 in exon 3 of ADARB2 gene was measured with targeted pyrosequencing in blood DNA samples collected from Finnish (33 pairs) and Swedish (29 pairs) twin pairs discordant for Alzheimer’s disease (AD). The association of the disease status with DNA methylation was examined with linear mixed effects model including gender, zygosity, age, and interaction terms as fixed effects and twin pair information nested with genomic position as a random effect. The country of origin was not associated with the CpG methylation level and was excluded from the final models. a The CpG methylation level in male and female controls (ctrl) and cases. Wald t value for disease association including both genders is 4.68, for males 6.10, and for females 1.17. b Influence of zygosity of CpG methylation difference between twin pairs discordant for AD. c Influence of age on the CpG methylation difference between AD discordant twin pairs. Influence of APOE genotype on the CpG methylation level was examined separately including only gender as a covariate. Only group ε33 and combined groups ε34/44 were included in the statistical analysis. The CpG methylation levels for d female and e male ctrls and cases in different APOE groups. f CpG methylation difference in AD discordant twin pairs before onset of the diseases (not predictive for disease outcome based on Cox mixed effects model). In b–f, the representative data for CpG site 6 in the region is shown, and in a, c, and f, the lines are the smoothed conditional means with 0.95 confidence intervals area