FIGURE 4.

HRs of incident T2D per 1% TEI increase in macronutrient intake, stratified by CAV2 rs2270188 genotype: comparison between Fisher et al. (35) and EPIC-InterAct. HRs from Fisher et al. (35) (top) and pooled HRs from EPIC-InterAct (bottom) for both total fat intake (A) and saturated fat intake (B). Fisher et al. (35) adjusted for sex, age, TEI, and BMI (P-interaction values were obtained using results from the confirmatory case-cohort study under the additive genetic model). The EPIC-Interact replication model was adjusted for age (equal to the underlying time scale), sex, center, TEI, and BMI, excluding the EPIC-InterAct Potsdam center. To note, the classical interaction model was adopted, not the genotype-specific model reported in Fisher et al. (35), because of the stated equivalence of the 2. P-interaction values were estimated by treating macronutrients and rs2270188 as continuous variables. In the EPIC-InterAct study, heterogeneity between countries was moderate (I² = 41% and 34% in panels A and B, respectively). The total sample size for the EPIC-InterAct analysis was 19,477. Multiplicative interaction analysis was performed using Prentice-weighted Cox regression. CAV2, caveolin 2; EPIC, European Prospective Investigation into Cancer; TEI, total energy intake; T2D, type 2 diabetes.