Definitive roles of TOMM40-APOE-APOC1 variants in the Alzheimer's risk.
Neurobiol Aging
; 110: 122-131, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34625307
ABSTRACT
Despite advances, the roles of genetic variants from the APOE-harboring 19q13.32 region in Alzheimer's disease (AD) remain controversial. We leverage a comprehensive approach to gain insights into a more homogeneous genetic architecture of AD in this region. We use a sample of 2,673 AD-affected and 16,246 unaffected subjects from 4 studies and validate our main findings in the landmark Alzheimer's Disease Genetics Consortium cohort (3,662 AD-cases and 1,541 controls). We report the remarkably high excesses of the AD risk for carriers of the ε4 allele who also carry minor alleles of rs2075650 (TOMM40) and rs12721046 (APOC1) polymorphisms compared to carriers of their major alleles. The exceptionally high 4.37-fold (p=1.34 × 10-3) excess was particularly identified for the minor allele homozygotes. The beneficial and adverse variants were significantly depleted and enriched, respectively, in the AD-affected families. This study provides compelling evidence for the definitive roles of the APOE-TOMM40-APOC1 variants in the AD risk.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
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Polimorfismo Genético
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Predisposição Genética para Doença
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Apolipoproteína C-I
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Estudos de Associação Genética
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Doença de Alzheimer
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Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial
Tipo de estudo:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2022
Tipo de documento:
Article