Titre :

Genetic architecture of sporadic frontotemporal dementia and overlap with alzheimer's and parkinson's diseases

Auteur(s) :

Ferrari, Raffaele [Auteur]
Wang, Yunpeng [Auteur]
Vandrovcova, Jana [Auteur]
Guelfi, Sebastian [Auteur]
Witeolar, Aree [Auteur]
Karch, Celeste M. [Auteur]
Schork, Andrew J. [Auteur]
Fan, Chun C. [Auteur]
Brewer, James B. [Auteur]
Momeni, Parastoo [Auteur]
Schellenberg, Gerard D. [Auteur]
Dillon, William P. [Auteur]
Sugrue, Leo P. [Auteur]
Hess, Christopher P. [Auteur]
Yokoyama, Jennifer S. [Auteur]
Bonham, Luke W. [Auteur]
Rabinovici, Gil D. [Auteur]
Miller, Bruce L. [Auteur]
Andreassen, Ole A. [Auteur]
Dale, Anders M. [Auteur]
Hardy, John [Auteur]
Desikan, Rahul S. [Auteur]

Titre de la revue :

Journal of neurology, neurosurgery, and psychiatry

Nom court de la revue :

J. Neurol. Neurosurg. Psychiatr.

Numéro :

88

Pagination :

152-164

Date de publication :

2017-02-01

ISSN :

1468-330X

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer's disease (AD) and Parkinson's disease (PD) has been suggested; however, the relationship between these disorders is still ...
Lire la suite >Clinical, pathological and genetic overlap between sporadic frontotemporal dementia (FTD), Alzheimer's disease (AD) and Parkinson's disease (PD) has been suggested; however, the relationship between these disorders is still not well understood. Here we evaluated genetic overlap between FTD, AD and PD to assess shared pathobiology and identify novel genetic variants associated with increased risk for FTD. Summary statistics were obtained from the International FTD Genomics Consortium, International PD Genetics Consortium and International Genomics of AD Project (n>75 000 cases and controls). We used conjunction false discovery rate (FDR) to evaluate genetic pleiotropy and conditional FDR to identify novel FTD-associated SNPs. Relevant variants were further evaluated for expression quantitative loci. We observed SNPs within the HLA, MAPT and APOE regions jointly contributing to increased risk for FTD and AD or PD. By conditioning on polymorphisms associated with PD and AD, we found 11 loci associated with increased risk for FTD. Meta-analysis across two independent FTD cohorts revealed a genome-wide signal within the APOE region (rs6857, 3'-UTR=PVRL2, p=2.21×10-12-7 Our findings demonstrate genetic pleiotropy in these neurodegenerative diseases and indicate that sporadic FTD is a polygenic disorder where multiple pleiotropic loci with small effects contribute to increased disease risk.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

CHU Lille
CNRS
Inserm
Université de Lille

Collections :

• Lille Neurosciences & Cognition (LilNCog) - U 1172

Équipe(s) de recherche :

Troubles cognitifs dégénératifs et vasculaires

Date de dépôt :

2019-11-27T14:30:10Z