Figure 4.

Trait iQTLs and mediated moderation

(A) Number of significant trait ieQTLs and imeQTLs in exam 1 and exam 5 (FDR < 0.25) by direction of the iQTL effect. For numeric traits, direction of the iQTL effect is defined as (1) positive—genotype effect size increases depending on the trait or (2) negative—genotype effect size decreases depending on the trait. For binary traits, the direction of the effect is defined as (1) no effect in one—nominally non-significant genotype effect in one of the groups, (2) magnitude difference—nominally significant genotype effect in both groups with the same sign of the estimate, or (3) opposite effect—nominally significant genotype effect in both groups with the opposite sign of the estimate.

(B) Example of smoking-current ieQTL for AHRR (upper plot) and age imeQTL for cg06953865 (lower plot); the p value of the interaction effect from the linear model fitted with TensorQTL is shown.

(C) Inflation of G × monocyte effect among age ieQTLs and G × neutrophil effect among age imeQTLs in exam 5 data by direction of age iQTL effect. λ is the inflation factor.

(D) Schema of the mediated-moderation approach, where the moderation effect of age on the genotype to DNAm association is mediated by changes in neutrophil proportions. The mediated-moderation effect is described by the G × age → G × neutrophil → DNAm path. p value histogram of the average causal mediation effect (ACME) of the G × neutrophil effect mediating the G × age effect on DNAm for 32 age imeQTLs with a positive or negative direction of effect.