Impact of sex, age, and ancestry on Apolipoprotein E‐APOE‐ risk for Alzheimer’s disease
Omar Garcia Rodriguez, Juan I. Young, Lily Wang, Eden R. Martin, Brian W. Kunkle,- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
Previous studies have reported that non‐Hispanic White (NHW) females carrying the APOE ε4 allele have an increased risk for developing AD when compared to men. Recently, analyses showed that the risk for developing AD may be equivalent for males and females but may differ by age. Few studies have been done on this issue in groups other than NHW. We aimed to evaluate the association between sex, age, ancestry, APOE, and AD.
Methods
We conducted a pooled case‐control study from 45 independent databases in Alzheimer’s Disease Genetics Consortium. Individuals (age≥55 years) were included (n = 31,058). Independent variables were age, sex, ancestry/ethnicity, and APOE genotype (ε3/ε4 vs. ε3/ε3). Logistic, linear, and Cox regression models were performed by sex and ancestry.
Results
Regardless of ancestry, men and women with APOE ε3/ε4 showed no significant difference in the risk of developing AD (all age groups combined). When comparing subjects with APOE ε3/ε4 to those with ε3/ε3, East‐Asian (EA) females (OR,4.90; 95% CI: 3.46‐6.95) had the strongest OR, followed by EA males (OR, 4.09: 2.67‐6.27); and NHW females (OR,3.40: 3.14‐3.68) and men (OR,3.33: 3.03‐3.66) among all ethnicities. When stratified by age, NHW females (OR, 3.41: 2.69‐4.32 vs. NHW males: OR,2.57: 1.94‐3.39) and EA women (OR,6.51: 1.31‐32.30 vs. EA men: OR,3.41: 0.66‐17.56) with APOE ε3/ε4 showed a higher risk of developing AD between ages 55‐65; whereas African American (AA) women (OR,4.14: 3.06‐5.60 vs. AA men: OR,2.27: 1.45‐3.55) exhibited this pattern later, at the age of 66‐75 years. In Hispanics, the pattern is reversed, with males aged 55‐65 years carrying APOE ε3/ε4 (OR,6.65; 1.64‐26.89: vs. females: OR,2.27; 1.03‐4.98) had a stronger association with AD risk than their female counterpart. Case‐only and survival analyses also showed that NHW and EA female carriers of APOE ε3/ε4 had an earlier age at the onset of AD than their counterpart in men.
Conclusions
Our findings suggest sex differences by age and ethnicity in the risk for developing AD and age at onset of AD for carriers of APOE ε4. Confirming these findings could lead to a better‐personalized risk assessment for AD that accounts for sex differences in APOE.