Fig. 2: Genetic influences on entorhinal cortex tau.

Lines show the estimated marginal levels of tau pathology for individuals with varying genetic profiles at different levels of amyloid beta (Aβ). Whisker plot in panel c shows estimated levels of entorhinal cortex tau (Tau_EC) pathology based on sex and Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) risk variant carrier status, marginalised over Aβ. Points represent estimated Tau_EC pathology derived from multiple linear regressions, and error bars indicate 95% two-sided confidence intervals computed from 1000 multiplier bootstrap replications. Different effects in the discovery sample (n = 626) for (a) Apolipoprotein E (APOE) -ε4, (b) sex, (c) interaction of sex and TREM2 risk variant carrier status. Different effects in the replication sample (n = 726) for (d) APOE-ε4 and (e) sex. f Causal path model to estimate Tau_EC. Solid lines indicate a direct effect of an upstream variable on a downstream pathology, dashed lines indicate an interactive effect between upstream variables (i.e. Aβ centiloid or genetic variable) on Tau_EC. Lines initiating from the black genetic variables box may indicate a direct or interactive effect of genetic variables on the outcome variable. Values in the parentheses indicate level of genetic variable (APOE-ε4 alleles (0,1,2) and TREM2 risk variant carrier status (0,1)). Source data are provided as a Source Data file.