Scientific Reports (Mar 2023)

Interaction analysis of ancestry-enriched variants with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging

  • Einat Granot-Hershkovitz,
  • Rui Xia,
  • Yunju Yang,
  • Brian Spitzer,
  • Wassim Tarraf,
  • Priscilla M. Vásquez,
  • Richard B. Lipton,
  • Martha Daviglus,
  • Maria Argos,
  • Jianwen Cai,
  • Robert Kaplan,
  • Myriam Fornage,
  • Charles DeCarli,
  • Hector M. Gonzalez,
  • Tamar Sofer

DOI
https://doi.org/10.1038/s41598-023-32028-2
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 9

Abstract

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Abstract 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.