On the effect heterogeneity of established disease susceptibility loci for Alzheimer's disease across different genetic ancestries.
Alzheimers Dement
; 20(5): 3397-3405, 2024 05.
Article
em En
| MEDLINE
| ID: mdl-38563508
ABSTRACT
INTRODUCTION:
Genome-wide association studies have identified numerous disease susceptibility loci (DSLs) for Alzheimer's disease (AD). However, only a limited number of studies have investigated the dependence of the genetic effect size of established DSLs on genetic ancestry.METHODS:
We utilized the whole genome sequencing data from the Alzheimer's Disease Sequencing Project (ADSP) including 35,569 participants. A total of 25,459 subjects in four distinct populations (African ancestry, non-Hispanic White, admixed Hispanic, and Asian) were analyzed.RESULTS:
We found that nine DSLs showed significant heterogeneity across populations. Single nucleotide polymorphism (SNP) rs2075650 in translocase of outer mitochondrial membrane 40 (TOMM40) showed the largest heterogeneity (Cochran's Q = 0.00, I2 = 90.08), followed by other SNPs in apolipoprotein C1 (APOC1) and apolipoprotein E (APOE). Two additional loci, signal-induced proliferation-associated 1 like 2 (SIPA1L2) and solute carrier 24 member 4 (SLC24A4), showed significant heterogeneity across populations.DISCUSSION:
We observed substantial heterogeneity for the APOE-harboring 19q13.32 region with TOMM40/APOE/APOC1 genes. The largest risk effect was seen among African Americans, while Asians showed a surprisingly small risk effect.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Predisposição Genética para Doença
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Polimorfismo de Nucleotídeo Único
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Estudo de Associação Genômica Ampla
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Doença de Alzheimer
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Proteínas do Complexo de Importação de Proteína Precursora Mitocondrial
Limite:
Aged
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article