Abstract
BackgroundThe prevalence and incidence of dementia are low in Nigeria, but high among African-Americans. In these populations there is a high frequency of the risk-conferring APOE-e4 allele, but the risk ratio is less than in Europeans. In an admixed population of older Cubans we explored the effects of ethnic identity and genetic admixture on APOE genotype, its association with dementia, and dementia prevalence.MethodsA cross-sectional catchment area survey of 2928 residents aged 65 and over, with a nested case-control study of individual admixture. Dementia diagnosis was established using 10/66 Dementia and DSM-IV criteria. APOE genotype was determined in 2520 participants, and genetic admixture in 235 dementia cases and 349 controls.ResultsMean African admixture proportions were 5.8% for 'white', 28.6% for 'mixed' and 49.6% for 'black' ethnic identities. All three groups were substantially admixed with considerable overlap. African admixture was linearly related to number of APOE-e4 alleles. One or more APOE-e4 alleles was associated with dementia in 'white' and 'black' but not 'mixed' groups but neither this, nor the interaction between APOE-e4 and African admixture (PR 0.52, 95% CI 0.13-2.08) were statistically significant. Neither ethnic identity nor African admixture was associated with dementia prevalence when assessed separately. However, considering their joint effects African versus European admixture was independently associated with a higher prevalence, and 'mixed' or 'black' identity with a lower prevalence of dementia.ConclusionsAPOE genotype is strongly associated with ancestry. Larger studies are needed to confirm whether the concentration of the high-risk allele in those with African ancestry is offset by an attenuation of its effect. Counter to our hypothesis, African admixture may be associated with higher risk of dementia. Although strongly correlated, effects of admixture and ethnic identity should be distinguished when assessing genetic and environmental contributions to disease risk in mixed ancestry populations.
Highlights
The prevalence and incidence of dementia are low in Nigeria, but high among African-Americans
Two longitudinal studies in the US suggest no association between APOE e4 and incident Alzheimer’s Disease (AD) among African Americans, while the incidence of AD seemed to be higher for African Americans in every APOE genotype [3,4]
We describe the proportions assigned to each ethnic identity (’white’, ‘mixed’ and ‘black’), and the weighted mean individual admixture proportions (European, African and Native American), and, in the subsample, test for an association between them using a weighted one way ANOVA
Summary
The prevalence and incidence of dementia are low in Nigeria, but high among African-Americans In these populations there is a high frequency of the risk-conferring APOE-e4 allele, but the risk ratio is less than in Europeans. In a case-control study in Florida the association between APOE e4 and AD was as strong for Cuban Americans as for white non-Hispanics [16] in contrast to the absence of an observed association among Hispanics in North Manhattan [4]. This pattern of findings is strongly suggestive of the presence of gene by environment, and/or gene by gene interactions [17]
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