These were based on associations in this sample between the variables significant in bivariate analyses (Supplementary Table 4) and the hypothesized directions of the associations were based on either the inherent nature of the variables (i.e. if there is a temporal association between age or sex with any of the biomarkers, age or sex would come first in the ordering) or hypotheses based on existing literature (i.e. the amyloid cascade hypothesis [51], GFAP being closely linked to amyloid pathology [52], and WMLs preceding brain atrophy [53]). This evidence concerns the gene GFAP and Brain atrophy.