A novel age-informed approach for genetic association analysis in Alzheimer's disease.
Alzheimers Res Ther
; 13(1): 72, 2021 04 01.
Article
en En
| MEDLINE
| ID: mdl-33794991
ABSTRACT
BACKGROUND:
Many Alzheimer's disease (AD) genetic association studies disregard age or incorrectly account for it, hampering variant discovery.METHODS:
Using simulated data, we compared the statistical power of several models logistic regression on AD diagnosis adjusted and not adjusted for age; linear regression on a score integrating case-control status and age; and multivariate Cox regression on age-at-onset. We applied these models to real exome-wide data of 11,127 sequenced individuals (54% cases) and replicated suggestive associations in 21,631 genotype-imputed individuals (51% cases).RESULTS:
Modeling variable AD risk across age results in 5-10% statistical power gain compared to logistic regression without age adjustment, while incorrect age adjustment leads to critical power loss. Applying our novel AD-age score and/or Cox regression, we discovered and replicated novel variants associated with AD on KIF21B, USH2A, RAB10, RIN3, and TAOK2 genes.CONCLUSION:
Our AD-age score provides a simple means for statistical power gain and is recommended for future AD studies.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Alzheimer
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Alzheimers Res Ther
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos