Table 4.
Mega-analysis of the effect of AD genetic risk factors on hippocampal and amygdala volume in the AD, MCI, and healthy older groups
| Participant group | Genetic variant/PRS | Mean hippocampus
|
Mean amygdala
|
||||||
|---|---|---|---|---|---|---|---|---|---|
| N | R2 | β (SE) | p | N | R2 | β (SE) | p | ||
| AD | APOE ɛ4 | 267 | 0.027 | −0.18 (0.04) | 1.1 × 10−4a | 268 | 0.008 | −0.11 (0.05) | 0.023 |
| PRS p < 5 × 10−8 | 279 | 0.000 | 0.00 (0.04) | 0.951 | 280 | 0.000 | −0.01 (0.05) | 0.760 | |
| PRS p < 1 × 10−6 | 279 | 0.000 | 0.00 (0.04) | 0.932 | 280 | 0.007 | −0.09 (0.05) | 0.053 | |
| PRS p < 1 × 10−4 | 279 | 0.000 | −0.02 (0.05) | 0.655 | 280 | 0.001 | −0.03 (0.05) | 0.512 | |
| PRS p < 1 × 10−3 | 279 | 0.001 | −0.03 (0.04) | 0.442 | 280 | 0.000 | −0.02 (0.05) | 0.718 | |
| PRS p < 0.01 | 279 | 0.001 | −0.02 (0.04) | 0.600 | 280 | 0.000 | −0.02 (0.05) | 0.705 | |
| PRS p < 0.05 | 279 | 0.000 | −0.01 (0.04) | 0.780 | 280 | 0.000 | 0.01 (0.05) | 0.860 | |
| PRS p < 0.1 | 279 | 0.000 | −0.01 (0.04) | 0.781 | 280 | 0.000 | 0.01 (0.05) | 0.825 | |
| PRS p < 0.5 | 279 | 0.000 | 0.00 (0.04) | 0.974 | 280 | 0.002 | 0.05 (0.05) | 0.278 | |
| PRS p < 1 | 279 | 0.000 | 0.01 (0.04) | 0.888 | 280 | 0.002 | 0.05 (0.05) | 0.281 | |
| TREM2 rs9394721 | 279 | 0.004 | −0.06 (0.04) | 0.166 | 280 | 0.000 | 0.01 (0.04) | 0.854 | |
| MCI | APOE ɛ4 | 621 | 0.024 | −0.16 (0.03) | 1.5 × 10−6b | 619 | 0.005 | −0.08 (0.03) | 0.012 |
| PRS p < 5 × 10−8 | 645 | 0.000 | −0.02 (0.03) | 0.649 | 643 | 0.000 | 0.02 (0.03) | 0.511 | |
| PRS p < 1 × 10−6 | 645 | 0.003 | −0.05 (0.03) | 0.121 | 643 | 0.000 | 0.00 (0.03) | 0.910 | |
| PRS p < 1 × 10−4 | 645 | 0.004 | −0.07 (0.03) | 0.057 | 643 | 0.001 | 0.03 (0.03) | 0.361 | |
| PRS p < 1 × 10−3 | 645 | 0.002 | −0.04 (0.03) | 0.192 | 643 | 0.000 | −0.01 (0.03) | 0.674 | |
| PRS p < 0.01 | 645 | 0.000 | 0.01 (0.03) | 0.687 | 643 | 0.000 | −0.01 (0.03) | 0.655 | |
| PRS p < 0.05 | 645 | 0.000 | 0.02 (0.03) | 0.572 | 643 | 0.000 | −0.02 (0.03) | 0.518 | |
| PRS p<0.1 | 645 | 0.000 | 0.01 (0.04) | 0.825 | 643 | 0.001 | −0.04 (0.03) | 0.248 | |
| PRS p < 0.5 | 645 | 0.000 | 0.01 (0.03) | 0.761 | 643 | 0.000 | −0.02 (0.03) | 0.612 | |
| PRS p < 1 | 645 | 0.000 | 0.01 (0.03) | 0.716 | 643 | 0.000 | −0.02 (0.03) | 0.607 | |
| TREM2 rs9394721 | 645 | 0.004 | −0.06 (0.03) | 0.047c | 643 | 0.000 | 0.00 (0.03) | 0.916 | |
| Healthy older | APOE ɛ4 | 723 | 0.000 | 0.00 (0.03) | 0.961 | 720 | 0.000 | −0.01 (0.03) | 0.775 |
| PRS p < 5 × 10−8 | 740 | 0.002 | −0.05 (0.03) | 0.157 | 737 | 0.001 | 0.02 (0.03) | 0.388 | |
| PRS p < 1 × 10−6 | 740 | 0.001 | −0.04 (0.03) | 0.289 | 737 | 0.000 | 0.02 (0.03) | 0.552 | |
| PRS p < 1 × 10−4 | 740 | 0.002 | −0.05 (0.03) | 0.126 | 737 | 0.001 | −0.03 (0.03) | 0.298 | |
| PRS p < 1 × 10−3 | 740 | 0.003 | −0.05 (0.03) | 0.075 | 737 | 0.000 | 0.02 (0.03) | 0.503 | |
| PRS p < 0.01 | 740 | 0.001 | −0.03 (0.03) | 0.331 | 737 | 0.000 | 0.01 (0.03) | 0.599 | |
| PRS p < 0.05 | 740 | 0.001 | −0.04 (0.03) | 0.228 | 737 | 0.001 | 0.03 (0.03) | 0.276 | |
| PRS p < 0.1 | 740 | 0.001 | −0.03 (0.03) | 0.416 | 737 | 0.001 | 0.03 (0.03) | 0.208 | |
| PRS p < 0.5 | 740 | 0.001 | −0.03 (0.03) | 0.363 | 737 | 0.000 | 0.01 (0.03) | 0.663 | |
| PRS p < 1 | 740 | 0.000 | −0.02 (0.03) | 0.490 | 737 | 0.000 | 0.00 (0.03) | 0.910 | |
| TREM2 rs9394721 | 740 | 0.004 | −0.06 (0.03) | 0.042 | 737 | 0.001 | −0.04 (0.03) | 0.165 | |
The AD group includes AD cases from ADNI and AddNeuromed; the MCI groups include those with MCI from ADNI, AddNeuroMed, Sydney MAS, and OATS; and healthy older includes healthy controls from ADNI and AddNeuroMed, and those with no diagnosis of MCI or dementia from Sydney MAS and OATS. p values are not correct for multiple testing. Associations with p < 0.05 are shown in bold.
Key: AD, Alzheimer’s disease; ADNI, Alzheimer’s Disease Neuroimaging Initiative; APOE, apolipoprotein E; MCI, mild cognitive impairment; OATS, Older Australian Twins Study; PRS, polygenic risk scores; QTIM, Queensland Twin Imaging; R2, the variance explained by the genotype; SE, standard error; Sydney MAS, Sydney Memory and Ageing Study.
Stronger association in females (N = 130, β = −0.27, p = 7.3 × 10−5) compared to males (N = 137, β = 0.11, p = 0.068).
Stronger association in females (N = 267, β = −0.21, p = 1.7 × 10−4) compared to males (N = 816, β = −0.01, p = 0.626).
Association found in those 75 years of age or younger (≤75 years; N = 292, β = −0.19, p = 0.003 and N = 353, β = 0.015, p = 0.699).