Figure 2.

Potential pathways linking genetic variants with Alzheimer’s dementia.

(1) A genetic variant exerts its effect on Alzheimer’s dementia, mediated completely by DNA methylation; (2) A genetic variant exerts its effect on Alzheimer’s dementia, mediated through DNA methylation which regulates gene expression; (3) A genetic variant exerts its effect on Alzheimer’s dementia, mediated completely by gene expression; (4) A genetic variant exerts its effect on Alzheimer’s dementia, mediated through gene expression which is regulated by DNA methylation; and (5) A genetic variant exerts its effect on Alzheimer’s dementia, mediated by genetic regulation of gene expression through DNA methylation.

mQTL and eQTL represent genetic variant that is associated with DNA methylation and gene expression, respectively. The top associated eQTLs or mQTLs that passed the default criteria (P_eQTL<5 × 10⁻⁸ or P_mQTL<5 × 10⁻⁸, with a default window size of 2000 Kb) were selected as the instrumental variables.

mQTL, DNA methylation quantitative trait loci; eQTL, gene expression quantitative trait loci.