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Exploring the role of Amerindian genetic ancestry and ApoEε4 gene on Alzheimer disease in the Peruvian population
Author(s) -
CornejoOlivas Mario R.,
Rajabli Farid,
VelizOtani Diego M.,
Whitehead Patrice L.,
Hofmann Natalia K.,
HamiltonNelson Kara L.,
IllanesManrique Maryenela,
MillaNeyra Karina,
Marca Victoria,
SarapuraCastro Elison,
RiveraValdivia Andrea,
Mejía Koni Katerin,
Adams Larry D.,
Mena Pedro Ramon,
Vance Jeffery M.,
Isasi Rosario,
Cuccaro Michael L.,
Beecham Gary W.,
MezaVega Maria,
CastroSuarez Sheila,
Custodio Nilton,
Montesinos Rosa,
Mazzetti Pilar,
PericakVance Margaret A
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045012
Subject(s) - apolipoprotein e , logistic regression , allele , demography , genotyping , population , ancestry informative marker , ethnic group , odds ratio , disease , genetic genealogy , genetic admixture , genetics , allele frequency , genotype , medicine , biology , gene , anthropology , sociology
Background The ApoEε4 allele is a major risk factor for AD whose effect shows strong racial/ethnic differences. Among the populations ApoE shows the strongest effect in East Asians (EA) (ε3/ε4 odds ratio OR: 3.1–5.6; ε4/ε4 OR: 11.8–33.1) and has a relatively lower effect in non‐Hispanic Whites (NHW) (ε3/ε4 OR: 3.2; ε4/ε4 OR: 14.9). The effect of ApoEε4 in populations with Amerindian (AI) ancestry is unknown. Peruvians with high AI (∼80%) genetic ancestry provide an opportunity to assess the effect of ApoEε4 in AD individuals with AI genetic ancestry. Our aim is to use data from the Peruvian population to assess the role of AI genetic ancestry and the ApoE gene on AD. Method Genotyping including both ApoE and Illumina GSA array was performed in 147 Peruvians (54 AD cases and 93 cognitively intact (CI) controls). PC‐AiR and model‐based ADMIXTURE approach inferred population structure. To assess local ancestry, phasing using SHAPEIT (with 1kGP reference) was followed by RFMix (HGDP reference panels). Association between affection status and ApoEε4 dose was analyzed using logistic regression, adjusting for age, gender, PC1‐3. Result Admixture analysis showed that Peruvians have a substantial AI (62%) ancestral component (31% European, 4% African and 3% EA genetic ancestry). AD individuals have higher frequency of ApoEε4 allele than CI individuals (7.4% vs 3.7%, respectively, p‐value = 3e‐4). Logistic regression analysis showed ApoE ε4 dose significantly associated with AD in Peruvians (OR = 4.92, CI: 2.07‐12.83, p = 6e‐4). The average of the local ancestry proportions around the ApoE were close to the average global ancestry proportions (AI:56%, EU:37% and AF:7%). Conclusion Our results showed that the risk for AD from ApoEε4 in Peruvians is higher than we have observed in NHW populations. Given the high admixture of AI in the Peruvian population, it suggests that the AI local ancestry is contributing to a strong risk for AD in ApoEε4 carriers. This would align with the current believed migration pattern of AI from East Asia, where ApoEε4 carriers have the highest ApoEε4 risk for AD. Further ascertainment is ongoing to identify additional AI ApoEε4 carriers to directly ascertain risk.