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APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two. We identified such variants in the APOE region with a predicted moderate impact based on the SnpEff tool. We tested their interaction with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) population and African Americans from the Atherosclerosis Risk In Communities (ARIC) study. We identified 5 Amerindian and 14 African enriched variants with an expected moderate effect. A suggestive significant interaction (p-value = 0.01) was found for one African-enriched variant, rs8112679, located in the ZNF222 gene fourth exon. Our results suggest there are no ancestry-enriched variants with large effect sizes of interaction effects with APOE-ɛ4 on MCI in the APOE region in the Hispanic/Latino population. Further studies are needed in larger datasets to identify potential interactions with smaller effect sizes. [ABSTRACT FROM AUTHOR]

The apoE4 isoform is associated with increased cholesterol, cardiovascular risk, and Alzheimer's Disease risk, however, its distribution is not well-understood among US Latinos. Latinos living in the US are highly Amerindian, European and African admixed, which varies by region and country of origin. However, Latino genetic diversity is understudied and consequently poorly understood, which has significant implications for understanding disease risk in nearly one-fifth of the US population. In this report we describe apoE distributions in a large and representative sample of diverse, genetically determined US Latinos. [ABSTRACT FROM AUTHOR]