Genetic associations with age at dementia onset in the PSEN1 E280A Colombian kindred.
Alzheimers Dement
; 19(9): 3835-3847, 2023 09.
Article
de En
| MEDLINE
| ID: mdl-36951251
ABSTRACT
INTRODUCTION:
Genetic associations with Alzheimer's disease (AD) age at onset (AAO) could reveal genetic variants with therapeutic applications. We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations.METHODS:
A genetic association study was conducted to examine ADAD AAO in 340 individuals with the PSEN1 E280A mutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic early-onset AD study and four late-onset AD studies.RESULTS:
13 variants had p<1×10-7 or p<1×10-5 with replication including three independent loci with candidate associations with clusterin including near CLU. Other suggestive associations were identified in or near HS3ST1, HSPG2, ACE, LRP1B, TSPAN10, and TSPAN14.DISCUSSION:
Variants with suggestive associations with AAO were associated with biological processes including clusterin, heparin sulfate, and amyloid processing. The detection of these effects in the presence of a strong mutation for ADAD reinforces their potentially impactful role.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Clusterine
/
Maladie d'Alzheimer
Type d'étude:
Diagnostic_studies
/
Prognostic_studies
/
Risk_factors_studies
Limites:
Humans
Pays/Région comme sujet:
America do sul
/
Colombia
Langue:
En
Journal:
Alzheimers Dement
Année:
2023
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique