Association between WWOX/MAF variants and dementia-related neuropathologic endophenotypes.
Neurobiol Aging
; 111: 95-106, 2022 03.
Article
en En
| MEDLINE
| ID: mdl-34852950
ABSTRACT
The genetic locus containing the WWOX and MAF genes was implicated as a clinical Alzheimer's disease (AD) risk locus in two recent large meta-analytic genome wide association studies (GWAS). In a prior GWAS, we identified a variant in WWOX as a suggestive risk allele for hippocampal sclerosis. We hypothesized that the WWOX/MAF locus may be preferentially associated with non-plaque- and non-tau-related neuropathological changes (NC). Data from research participants with GWAS and autopsy measures from the National Alzheimer's Coordinating Center and the Religious Orders Study and the Rush Memory and Aging Project were meta-analyzed. Notably, no variants in the locus were significantly associated with ADNC. However, several WWOX/MAF variants had significant adjusted associations with limbic-predominant age-related TDP-43 encephalopathy NC (LATE-NC), HS, and brain arteriolosclerosis. These associations remained largely unchanged after adjustment for ADNC (operationalized with standard semiquantitative staging), suggesting that these associations are independent of ADNC. Thus, WWOX genetic variants were associated pathologically with LATE-NC, not ADNC.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fenotipo
/
Variación Genética
/
Proteínas Supresoras de Tumor
/
Demencia
/
Proteínas Proto-Oncogénicas c-maf
/
Estudio de Asociación del Genoma Completo
/
Proteinopatías TDP-43
/
Enfermedad de Alzheimer
/
Oxidorreductasa que Contiene Dominios WW
Tipo de estudio:
Risk_factors_studies
Límite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Neurobiol Aging
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos