Table 3.
Association results and heterogeneity estimates for metabolites in relation to A-T-N biomarkers stratified by APOE ε4 status.
| Biomarker/metabolite | Pooled effect | Pooled p value | Effect type | ε4+effect | ε4+p value | ε4− effect | ε4− p value | ε4 diff. statistic | ε4 diff. p value | ε4 diff. I² | Interaction p value |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pathological CSF Aβ1–42 | |||||||||||
| PC ae C44:6 | 0.283 | 2.58E-04 | Specific to ε4+ | 0.630 | 2.50E-05 | 0.158 | 7.96E-02 | −2.705 | 6.83E-03 | 63.030 | 2.80E-03 |
| PC ae C44:4 | 0.265 | 4.57E-04 | Specific to ε4+ | 0.565 | 1.30E-04 | 0.139 | 1.13E-01 | −2.478 | 1.32E-02 | 59.645 | 5.80E-03 |
| PC ae C44:5 | 0.260 | 5.23E-04 | Specific to ε4+ | 0.609 | 2.64E-05 | 0.129 | 1.37E-01 | −2.837 | 4.56E-03 | 64.749 | 3.07E-03 |
| PC ae C42:4 | 0.242 | 1.98E-03 | Specific to ε4+ | 0.564 | 1.32E-04 | 0.114 | 2.15E-01 | −2.589 | 9.61E-03 | 61.382 | 5.64E-03 |
| Proline | −0.075 | 3.52E-01 | Heterogeneous | 0.176 | 2.15E-01 | −0.202 | 4.40E-02 | −2.173 | 2.98E-02 | 53.982 | 1.58E-01 |
| Glycine | 0.060 | 4.60E-01 | Heterogeneous | 0.363 | 1.83E-02 | −0.102 | 3.05E-01 | −2.538 | 1.11E-02 | 60.604 | 7.89E-04 |
| FDG-PET | |||||||||||
| PC aa C32:1 | −0.127 | 2.32E-05 | Homogeneous | −0.087 | 5.35E-02 | −0.162 | 1.34E-04 | −1.210 | 2.26E-01 | 17.332 | 3.58E-01 |
| PC ae C44:4 | −0.111 | 2.27E-04 | Homogeneous | −0.115 | 1.39E-02 | −0.114 | 6.34E-03 | 0.023 | 9.82E-01 | 0.000 | 8.63E-01 |
| PC ae C44:5 | −0.105 | 4.07E-04 | Homogeneous | −0.122 | 8.34E-03 | −0.102 | 1.30E-02 | 0.326 | 7.44E-01 | 0.000 | 6.39E-01 |
| PC aa C32:0 | −0.107 | 6.85E-04 | Homogeneous | −0.135 | 4.39E-03 | −0.082 | 6.58E-02 | 0.818 | 4.14E-01 | 0.000 | 3.69E-01 |
| PC ae C42:4 | −0.103 | 8.56E-04 | Homogeneous | −0.131 | 5.79E-03 | −0.086 | 4.51E-02 | 0.701 | 4.83E-01 | 0.000 | 3.98E-01 |
| C10 | −0.057 | 5.14E-02 | Specific to ε4− | 0.037 | 4.17E-01 | −0.135 | 7.17E-04 | −2.840 | 4.51E-03 | 64.793 | 4.96E-03 |
| C8 | −0.051 | 9.96E-02 | Heterogeneous | 0.038 | 4.04E-01 | −0.138 | 1.58E-03 | −2.794 | 5.20E-03 | 64.215 | 6.37E-03 |
| Valine | 0.036 | 2.49E-01 | Heterogeneous | −0.040 | 4.08E-01 | 0.106 | 1.68E-02 | 2.234 | 2.55E-02 | 55.233 | 9.50E-02 |
| Glycine | −0.032 | 3.00E-01 | Heterogeneous | −0.140 | 3.05E-03 | 0.059 | 1.80E-01 | 3.092 | 1.99E-03 | 67.653 | 3.29E-03 |
| Proline | −0.023 | 4.51E-01 | Heterogeneous | −0.100 | 3.39E-02 | 0.048 | 2.64E-01 | 2.324 | 2.01E-02 | 56.977 | 6.35E-02 |
Associations of metabolites identified in the sex-centric analysis with A-T-N biomarkers that are either Bonferroni-significant in the full sample, in APOE ε4+ or APOE ε4− participants, or show nominal significance both in one APOE ε4 status group and for effect heterogeneity or the APOE ε4 status×metabolite interaction. Given are regression results for the full sample and both APOE ε4 status groups, as well as heterogeneity estimates and the p value for APOE ε4 status×metabolite interactions. Full association results for all strata are provided in Supplementary Data 2. ε4 diff. results from the heterogeneity analysis.