Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros

Banco de datos
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Int J Mol Sci ; 24(2)2023 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-36674414

RESUMEN

Mosaic loss of chromosome Y (mLOY) is a common ageing-related somatic event and has been previously associated with Alzheimer's disease (AD). However, mLOY estimation from genotype microarray data only reflects the mLOY degree of subjects at the moment of DNA sampling. Therefore, mLOY phenotype associations with AD can be severely age-confounded in the context of genome-wide association studies. Here, we applied Mendelian randomisation to construct an age-independent mLOY polygenic risk score (mloy-PRS) using 114 autosomal variants. The mloy-PRS instrument was associated with an 80% increase in mLOY risk per standard deviation unit (p = 4.22 × 10-20) and was orthogonal with age. We found that a higher genetic risk for mLOY was associated with faster progression to AD in men with mild cognitive impairment (hazard ratio (HR) = 1.23, p = 0.01). Importantly, mloy-PRS had no effect on AD conversion or risk in the female group, suggesting that these associations are caused by the inherent loss of the Y chromosome. Additionally, the blood mLOY phenotype in men was associated with increased cerebrospinal fluid levels of total tau and phosphorylated tau181 in subjects with mild cognitive impairment and dementia. Our results strongly suggest that mLOY is involved in AD pathogenesis.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Masculino , Femenino , Enfermedad de Alzheimer/genética , Cromosomas Humanos Y/genética , Estudio de Asociación del Genoma Completo , Mosaicismo , Factores de Riesgo , Disfunción Cognitiva/genética , Proteínas tau/genética , Biomarcadores , Péptidos beta-Amiloides/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA