Table 4.
Association results and heterogeneity estimates for metabolites in relation to A-T-N biomarkers in APOE ε4 carriers stratified by sex.
| Biomarker/metabolite | Pooled effect | Pooled p value | Sex diff. p value | Sex diff. I² | ε4 diff. p value | ε4 diff. I² | ε4+ (m) effect | ε4+ (m) p value | ε4+ (f) effect | ε4+ (f) p value |
|---|---|---|---|---|---|---|---|---|---|---|
| Pathological CSF Aβ1–42 | ||||||||||
| PC ae C44:6 | 0.283 | 2.58E-04 | 9.15E-01 | 0.000 | 6.83E-03 | 63.03 | 0.463 | 1.68E-02 | 0.922 | 1.90E-04 |
| PC ae C44:5 | 0.26 | 5.23E-04 | 6.01E-01 | 0.000 | 4.56E-03 | 64.749 | 0.521 | 6.17E-03 | 0.761 | 8.29E-04 |
| PC ae C42:4 | 0.242 | 1.98E-03 | 7.58E-01 | 0.000 | 9.61E-03 | 61.382 | 0.42 | 3.15E-02 | 0.761 | 8.65E-04 |
| CSF p-tau | ||||||||||
| C10 | 0.084 | 4.58E-03 | 2.76E-02 | 54.613 | 6.16E-01 | 0 | -0.064 | 3.24E-01 | 0.264 | 1.21E-04 |
| FDG-PET | ||||||||||
| Proline | −0.023 | 4.51E-01 | 4.50E-03 | 64.801 | 2.01E-02 | 56.977 | 0.046 | 4.76E-01 | −0.272 | 8.22E-05 |
Significant metabolite effects in the combined stratification (sex by APOE ε4 status) on A-T-N biomarkers are driven by or limited to APOE ε4+ females. Given are regression results for the full sample, APOE ε4+ males, APOE ε4+ females, as well as heterogeneity estimates by sex and APOE ε4 status. The only metabolite showing effect heterogeneity for both stratification variables was proline in its association with FDG-PET values. Full association results for all strata are provided in Supplementary Data 2. Sex diff. results from the sex-stratified heterogeneity analysis, ε4 diff. results from the APOE ε4 status-stratified heterogeneity analysis,ε4+ (m)/ε4+ (f) results for APOE ε4+ males and females, respectively.