Interactions between genetic admixture, ethnic identity, APOE genotype and dementia prevalence in an admixed Cuban sample; a cross-sectional population survey and nested case-control study

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.

Apolipoprotein-E genotype and human immunodeficiency virus-associated neurocognitive disorder: the modulating effects of older age and disease severity

“…The current study was comprised of 28.6% African Americans, 12% Latinos, 55.2% Caucasians, and 4.2% “others”, and differs from both Chang et al 25 and Spector et al 29 There is evidence to suggest that the risk for conferring the ε4 allele differs between ethnic distributions, as does the strength of the relationship between the ε4 allele and dementia. 43,44 Compared to Caucasians, the association between APOE genotype and dementia has been found to be weaker among African American and Hispanic samples. Conversely, a stronger association has been seen in Japanese participants.…”

“…First, in order to assess the effects of the ε4 allele on neurocognitive diagnosis, Chi-squared statistics were conducted for each of the age groups (<50 years versus ≥50 years) separately. Given the potential of ethnic admixture confounding these analyses, 43,44 we also reran these analyses with the Caucasian sample alone. We did not rerun these analyses with the African American sample because of reduced sample size.…”

Apolipoprotein E and Change in Episodic Memory in Blacks and Whites

“…Given that Blacks represent an admixed population with significant genetic contributions from both African and European ancestors (61), it is possible that genetic susceptibility related to the APOE ε4 allele is inconsistently expressed because there are other protective genetic factors in West African genomes that contributed to the genomes of modern Blacks. For example, a recent study reported a trend for the association between APOE genotype and dementia to be weaker in those with greater degrees of African admixture (62). Additional longitudinal studies with diverse populations are needed to test these and other hypotheses.…”

High proportion of mannosidosis and fucosidosis among lysosomal storage diseases in Cuba

“…Recent studies have demonstrated the important European/African contribution to the genetic composition of the Cuban population, indicating that admixture must be considered (Mendizabal et al, 2008;Cintado et al, 2009;Teruel et al, 2011). Thus, in analyzing the differences between the frequencies of individual LSDs found here and those of other studies, one has to take into account, not only the level of consanguinity and the possible genetic specificities of different populations, which occur worldwide, but also the genetic admixture of the Cuban population, not present in other epidemiological studies.…”