Skip to main content
. Author manuscript; available in PMC: 2017 Apr 1.
Published in final edited form as: Neurobiol Aging. 2016 Jan 11;40:68–77. doi: 10.1016/j.neurobiolaging.2015.12.023

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.

a

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).

b

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).

c

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).