Rare genetic variants correlate with better processing speed.
Neurobiol Aging
; 125: 115-122, 2023 05.
Article
em En
| MEDLINE
| ID: mdl-36813607
ABSTRACT
We conducted a genome-wide association study of Digit Symbol Substitution Test scores administered in 4207 family members of the Long Life Family Study (LLFS). Genotype data were imputed to the HRC panel of 64,940 haplotypes resulting in â¼15M genetic variants with a quality score > 0.7. The results were replicated using genetic data imputed to the 1000 Genomes phase 3 reference panel from 2 Danish twin cohorts the study of Middle Aged Danish Twins and the Longitudinal Study of Aging Danish Twins. The genome-wide association study in LLFS discovered 18 rare genetic variants (minor allele frequency (MAF) < 1.0%) that reached genome-wide significance (p-value < 5 × 10-8). Among these, 17 rare variants in chromosome 3 had large protective effects on the processing speed, including rs7623455, rs9821776, rs9821587, rs78704059, which were replicated in the combined Danish twin cohort. These SNPs are located in/near 2 genes, THRB and RARB, that belonged to the thyroid hormone receptors family that may influence the speed of metabolism and cognitive aging. The gene-level tests in LLFS confirmed that these 2 genes are associated with processing speed.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Estudo de Associação Genômica Ampla
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Velocidade de Processamento
Tipo de estudo:
Observational_studies
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Risk_factors_studies
Limite:
Humans
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Middle aged
Idioma:
En
Revista:
Neurobiol Aging
Ano de publicação:
2023
Tipo de documento:
Article