Table 2. Genetic association of KL-VSHET+ with AD endophenotypes in cognitively normal participants aged 60–80 years, stratified by APOE ε4 status.
| Modality | Group | CN participants | Odds ratio | Estimate | P value |
|---|---|---|---|---|---|
| (KL-VSHET+ %) | |||||
| Amyloid PET | APOE4+ | 1328 (27.5) | 0.94 | -0.07 | 0.61 |
| APOE4- | 2397 (26.5) | 0.99 | -0.01 | 0.90 | |
| Aβ42 | APOE4+ | 308 (26.3) | 0.67 | 0.72 | 0.007 |
| APOE4- | 722 (26.3) | 0.61 | 0.46 | 0.03 | |
| Tau | APOE4+ | 308 (26.9) | 0.39 | -0.94 | 0.007 |
| APOE4- | 722 (26.5) | 0.85 | -0.16 | 0.49 | |
| pTau | APOE4+ | 308 (26.9) | 0.50 | -0.68 | 0.04 |
| APOE4- | 722 (26.3) | 0.89 | -0.11 | 0.61 | |
| sTREM2 | APOE4+ | 199 (31.2) | 1.08 | 0.08 | 0.80 |
| APOE4- | 440 (25.2) | 1.20 | 0.18 | 0.43 |
Association between KL-VSHET+ and different dichotomized AD endophenotypes were assessed using logistic regression model. We used dichotomized endophenotype as the response variable, whereas, age, sex, and first three genetic PCs were used as covariates in an APOE4-stratified analysis. Significant associations are represented by bold P-values. Abbreviations: KL-VSHET+, Klotho-VS heterozygous; CN, cognitively normal; AD, Alzheimer’s disease; Std. Error, Standard error; %, percentage; Aβ, β-amyloid; pTau, phosphorylated tau181; soluble triggering receptor expressed on myeloid cells 2, sTREM2.