Table 5.
Influence of Single SNPs and Cumulative Genetic Risk Score on Neuroimaging Measuresa
| SNP | Gene | Coefficient (SE) | P Value | FDR-Corrected P Value |
|---|---|---|---|---|
| White matter lesion volume | ||||
| ε4 | APOE | 0.025 (0.033) | .44 | .44 |
| rs11136000 | CLU | −0.030 (0.031) | .31 | .32 |
| rs3851179 | PICALM | −0.005 (0.032) | .97 | .98 |
| rs1408077 | CR1 | 0.028 (0.039) | .45 | .46 |
| rs10501927 | CNTN5 | 0.119 (0.037) | .002 | .002 |
| rs7561528 | BIN1 | 0.017 (0.032) | .50 | .51 |
| Genetic risk score quartiles | 0.043 (0.015) | .04 | .04 | |
| Hippocampal volume | ||||
| ε4 | APOE | −0.240 (0.030) | 0.9 × 10−14 | 1.3 × 10−14 |
| rs11136000 | CLU | −0.019 (0.030) | .78 | .79 |
| rs3851179 | PICALM | 0.061 (0.029) | .04 | .05 |
| rs1408077 | CR1 | −0.037 (0.038) | .32 | .32 |
| rs10501927 | CNTN5 | −0.046 (0.036) | .17 | .19 |
| rs7561528 | BIN1 | −0.055 (0.031) | .06 | .08 |
| Genetic risk score quartiles | −0.099 (0.014) | .001 | .002 | |
| Amygdala volume | ||||
| ε4 | APOE | −0.079 (0.012) | 3.6 × 10−11 | 3.9 × 10−11 |
| rs11136000 | CLU | −0.018 (0.012) | .11 | .12 |
| rs3851179 | PICALM | 0.009 (0.012) | .47 | .47 |
| rs1408077 | CR1 | −0.017 (0.014) | .21 | .22 |
| rs10501927 | CNTN5 | −0.018 (0.013) | .19 | .19 |
| rs7561528 | BIN1 | −0.020 (0.012) | .09 | .10 |
| Genetic risk score quartiles | 0.043 (0.015) | .02 | .02 | |
| Entorhinal cortex thickness | ||||
| ε4 | APOE | −0.127 (0.026) | 8.7 × 10−7 | 9.1 × 10−7 |
| rs11136000 | CLU | −0.011 (0.025) | .65 | .67 |
| rs3851179 | PICALM | 0.066 (0.021) | .01 | .01 |
| rs1408077 | CR1 | −0.067 (0.031) | .03 | .03 |
| rs10501927 | CNTN5 | −0.067 (0.025) | .02 | .02 |
| rs7561528 | BIN1 | −0.121 (0.025) | .004 | .01 |
| Genetic risk score quartiles | −0.048 (0.011) | 7.9 × 10−4 | 8.4 × 10−4 | |
| Parahippocampal gyrus cortex thickness | ||||
| ε4 | APOE | −0.063 (0.017) | 3.3 × 10−4 | 3.8 × 10−4 |
| rs11136000 | CLU | 0.007 (0.017) | .66 | .67 |
| rs3851179 | PICALM | 0.014 (0.017) | .29 | .30 |
| rs1408077 | CR1 | 0.0004 (0.021) | .98 | .98 |
| rs10501927 | CNTN5 | −0.040 (0.019) | .05 | .05 |
| rs7561528 | BIN1 | −0.019 (0.017) | .24 | .24 |
| Genetic risk score quartiles | −0.022 (0.010) | .04 | .04 | |
| Temporal pole cortex thickness | ||||
| ε4 | APOE | −0.061 (0.019) | .002 | .004 |
| rs11136000 | CLU | −0.011 (0.018) | .50 | .51 |
| rs3851179 | PICALM | 0.033 (0.017) | .06 | .06 |
| rs1408077 | CR1 | −0.031 (0.024) | .12 | .14 |
| rs10501927 | CNTN5 | −0.051 (0.022) | .02 | .02 |
| rs7561528 | BIN1 | −0.041 (0.019) | .02 | .03 |
| Genetic risk score quartiles | −0.025 (0.009) | 8.2 × 10−4 | .001 | |
Abbreviations: FDR, false discovery rate; SNP, single-nucleotide polymorphism.
a
SNPs were selected based on results of prior genome-wide association studies4,5 with P < .001. Results are not shown for 11 SNPs at novel candidate loci with P > .05. The genetic risk score includes all (5 of 16) SNPs outside the APOE locus achieving P < .05 in ordinal logistic regression. All analyses are adjusted for age, sex, history of hypertension, education level (<13, 13–16, or >16 years), alcohol abuse, smoking (ever smoker status), and principal components 1 and 2. Analyses for SNPs outside the APOE locus were also adjusted for APOE genotypes (number of ε2 and ε4 copies).