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. 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 3.

Mega-analysis of the effect of AD genetic risk factors on hippocampal and amygdala volume in older and young adults

Participant group Genetic variant/PRS Mean hippocampus
Mean amygdala
N R2 β (SE) p N R2 β (SE) p
All older APOE ɛ4 1611 0.011 −0.11 (0.02) 8.7 × 10−9a 1607 0.003 −0.05 (0.02) 0.004
PRS p < 5 × 10−8 1664 0.000 −0.02 (0.02) 0.229 1660 0.000 0.02 (0.02) 0.381
PRS p < 1 × 10−6 1664 0.002 −0.04 (0.02) 0.030 1660 0.000 −0.01 (0.02) 0.607
PRS p < 1 × 10−4 1664 0.003 −0.05 (0.02) 0.004 1660 0.000 −0.01 (0.02) 0.746
PRS p < 1 × 10−3 1664 0.002 −0.05 (0.02) 0.007b 1660 0.000 0.01 (0.02) 0.633
PRS p < 0.01 1664 0.000 −0.02 (0.02) 0.246 1660 0.000 0.00 (0.02) 0.919
PRS p < 0.05 1664 0.000 −0.02 (0.02) 0.315 1660 0.000 0.00 (0.02) 0.819
PRS p < 0.1 1664 0.000 −0.02 (0.02) 0.369 1660 0.000 0.01 (0.02) 0.793
PRS p < 0.5 1664 0.000 −0.01 (0.02) 0.480 1660 0.000 0.01 (0.02) 0.580
PRS p < 1 1664 0.000 −0.01 (0.02) 0.663 1660 0.000 0.01 (0.02) 0.725
TREM2 rs9394721 1664 0.004 −0.06 (0.02) 0.001c 1660 0.000 −0.02 (0.02) 0.389
Young Adults APOE ɛ4 401 0.000 0.02 (0.04) 0.653 404 0.006 −0.08 (0.05) 0.120
PRS P < 5 × 10−8 447 0.004 −0.06 (0.04) 0.126 450 0.006 −0.08 (0.05) 0.091
PRS p < 1 × 10−6 447 0.000 0.01 (0.04) 0.801 450 0.000 0.02 (0.05) 0.656
PRS p < 1 × 10−4 447 0.002 −0.04 (0.04) 0.291 450 0.001 0.03 (0.05) 0.522
PRS p < 1 × 10−3 447 0.004 −0.06 (0.04) 0.111 450 0.000 0.02 (0.05) 0.734
PRS p < 0.01 447 0.000 −0.02 (0.04) 0.646 450 0.001 0.03 (0.05) 0.468
PRS p < 0.05 447 0.001 0.02 (0.04) 0.562 450 0.002 0.04 (0.05) 0.351
PRS p < 0.1 447 0.000 0.02 (0.04) 0.651 450 0.002 0.04 (0.05) 0.395
PRS p < 0.5 447 0.000 0.00 (0.04) 0.972 450 0.000 −0.02 (0.05) 0.687
PRS p < 1 447 0.000 0.00 (0.04) 0.996 450 0.000 −0.02 (0.05) 0.690
TREM2 rs9394721 447 0.000 0.00 (0.04) 0.991 450 0.000 0.00 (0.05) 0.921

The combined all-older group comprises the 4 elderly cohorts (ADNI, AddNeuroMed, OATS, and Sydney MAS, including those with AD, MCI, and healthy older). Cohort and disease status included as covariates along with standard covariates. The young adult group comprises the QTIM cohort. Significant associations are shown in bold.

Key: β, standardized beta; 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/PRS; SE, standard error; Sydney MAS, Sydney Memory and Ageing Study.

a

Stronger association in females (N = 817, β = −0.15, p = 3.4 × 10−8) compared to males (N = 794, β = −0.08, p = 0.004).

b

Association driven by females (Females; N = 848, β = −0.08, p = 0.001 and Males; N = 816, β = −0.01, p = 0.626).

c

Association found in those 75 years of age or younger (≤75 years: N = 791, β = −0.10, p = 3.4 × 10−4; >75 years; N = 873, β = 0.028, p = 0.240).