Table 2.
Association results and heterogeneity estimates for metabolites in relation to A-T-N biomarkers stratified by sex.
| Biomarker/metabolite | Pooled effect | Pooled p value | Effect type | Males effect | Males p value | Females effect | Females p value | Sex diff. statistic | Sex diff. p value | Sex diff. I² | Interaction p value |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Pathological CSF Aβ1–42 | |||||||||||
| PC ae C44:6 | 0.283 | 2.58E-04 | Homogeneous | 0.282 | 5.96E-03 | 0.299 | 1.33E-02 | −0.107 | 9.15E-01 | 0.000 | 8.09E-01 |
| PC ae C44:4 | 0.265 | 4.57E-04 | Homogeneous | 0.274 | 6.29E-03 | 0.255 | 3.07E-02 | 0.119 | 9.05E-01 | 0.000 | 7.83E-01 |
| PC ae C44:5 | 0.260 | 5.23E-04 | Homogeneous | 0.294 | 3.26E-03 | 0.214 | 6.38E-02 | 0.522 | 6.01E-01 | 0.000 | 4.34E-01 |
| Threonine | 0.207 | 6.72E-03 | Male-specific | 0.372 | 8.83E-04 | 0.070 | 5.17E-01 | 1.943 | 5.20E-02 | 48.545 | 4.03E-02 |
| Valine | −0.134 | 1.05E-01 | Heterogeneous | 0.032 | 7.80E-01 | −0.299 | 1.50E-02 | 1.973 | 4.85E-02 | 49.322 | 7.65E-02 |
| CSF p-tau | |||||||||||
| C10 | 0.084 | 4.58E-03 | Female-specific | 0.014 | 7.34E-01 | 0.144 | 6.07E-04 | −2.203 | 2.76E-02 | 54.613 | 2.55E-02 |
| C5−DC (C6−OH) | 0.103 | 2.35E-02 | Heterogeneous | 0.012 | 8.52E-01 | 0.205 | 2.27E-03 | −2.116 | 3.44E-02 | 52.740 | 3.38E-01 |
| C8 | 0.064 | 3.42E-02 | Heterogeneous | 0.003 | 9.39E-01 | 0.127 | 5.11E-03 | −2.028 | 4.26E-02 | 50.692 | 5.63E-02 |
| PC ae C36:2 | 0.056 | 8.65E-02 | Heterogeneous | 0.129 | 4.80E-03 | −0.023 | 6.18E-01 | 2.355 | 1.85E-02 | 57.535 | 2.16E-02 |
| Histidine | −0.034 | 2.72E-01 | Heterogeneous | 0.033 | 4.39E-01 | −0.105 | 1.97E-02 | 2.237 | 2.53E-02 | 55.290 | 2.42E-02 |
| Asparagine | 0.034 | 2.84E-01 | Heterogeneous | 0.107 | 1.66E-02 | −0.052 | 2.32E-01 | 2.550 | 1.08E-02 | 60.788 | 2.16E-02 |
| SM (OH) C16:1 | 0.032 | 3.10E-01 | Heterogeneous | 0.091 | 3.36E-02 | −0.039 | 3.99E-01 | 2.066 | 3.89E-02 | 51.592 | 3.75E-02 |
| Glycine | 0.030 | 3.50E-01 | Heterogeneous | 0.104 | 3.94E-02 | −0.026 | 5.23E-01 | 2.014 | 4.40E-02 | 50.346 | 6.88E-02 |
| PC ae C36:1 | 0.028 | 3.68E-01 | Heterogeneous | 0.088 | 4.17E-02 | −0.041 | 3.51E-01 | 2.094 | 3.62E-02 | 52.251 | 3.76E-02 |
| C2 | 0.015 | 5.85E-01 | Heterogeneous | −0.054 | 1.67E-01 | 0.089 | 3.02E-02 | −2.527 | 1.15E-02 | 60.430 | 1.39E-02 |
| FDG-PET | |||||||||||
| PC aa C32:1 | −0.127 | 2.32E-05 | Homogeneous | −0.140 | 6.31E-04 | −0.110 | 1.50E-02 | −0.499 | 6.18E-01 | 0.000 | 5.53E-01 |
| PC ae C44:4 | −0.111 | 2.27E-04 | Homogeneous | −0.097 | 1.80E-02 | −0.141 | 1.84E-03 | 0.716 | 4.74E-01 | 0.000 | 2.21E-01 |
| PC ae C44:5 | −0.105 | 4.07E-04 | Homogeneous | −0.112 | 5.80E-03 | −0.111 | 1.30E-02 | −0.021 | 9.83E-01 | 0.000 | 6.02E-01 |
| PC aa C32:0 | −0.107 | 6.85E-04 | Homogeneous | −0.125 | 5.67E-03 | −0.091 | 4.25E-02 | −0.547 | 5.84E-01 | 0.000 | 7.44E-01 |
| PC ae C42:4 | −0.103 | 8.56E-04 | Homogeneous | −0.103 | 1.58E-02 | −0.112 | 1.33E-02 | 0.156 | 8.76E-01 | 0.000 | 4.48E-01 |
| C16:1 | −0.103 | 9.09E-04 | Male-specific | −0.165 | 9.64E-05 | −0.029 | 5.38E-01 | −2.179 | 2.93E-02 | 54.107 | 9.94E-02 |
| PC ae C40:2 | −0.053 | 7.82E-02 | Heterogeneous | −0.119 | 4.34E-03 | 0.016 | 7.15E-01 | −2.238 | 2.52E-02 | 55.312 | 5.78E-02 |
| Proline | −0.023 | 4.51E-01 | Heterogeneous | 0.059 | 1.77E-01 | −0.118 | 8.18E-03 | 2.841 | 4.50E-03 | 64.801 | 7.74E-03 |
Metabolite associations with A-T-N biomarkers that are either Bonferroni-significant in the full sample, in one sex, or show nominal significance both in one sex and for effect heterogeneity or the sex×metabolite interaction term. Given are regression results for the full sample and both sexes, as well as heterogeneity estimates and the p value for sex×metabolite interactions. Full association results for all strata are provided in Supplementary Data 2. Sexdiff. results from the heterogeneity analysis.