Autor(es):
Cacace, Rita ; Van den Bossche, Tobi ; Engelborghs, Sebastiaan ; Geerts, Nathalie ; Laureys, Annelies ; Dillen, Lubina ; Graff, Caroline ; Thonberg, Håkan ; Chiang, Huei-Hsin ; Pastor, Pau ; Ortega-Cubero, Sara ; Pastor, Maria A. ; Diehl-Schmid, Janine ; Alexopoulos, Panagiotis ; Benussi, Luisa ; Ghidoni, Roberta ; Binetti, Giuliano ; Nacmias, Benedetta ; Sorbi, Sandro ; Sanchez-Valle, Raquel ; Lladó, Albert ; Gelpi, Ellen ; Almeida, Maria Rosário ; Santana, Isabel ; Tsolaki, Magda ; Koutroumani, Maria ; Clarimon, Jordi ; Lleó, Alberto ; Fortea, Juan ; De Mendonça, Alexandre ; Martins, Madalena ; Borroni, Barbara ; Padovani, Alessandro ; Matej, Radoslav ; Rohan, Zdenek ; Vandenbulcke, Mathieu ; Vandenberghe, Rik ; De Deyn, Peter P. ; Cras, Patrick ; van der Zee, Julie ; Sleegers, Kristel ; Van Broeckhoven, Christine
Data: 2015
Identificador Persistente: http://hdl.handle.net/10451/53458
Origem: Repositório da Universidade de Lisboa
Assunto(s): Alzheimer dementia; EOAD; PLD3; Meta-analysis; Next-generation sequencing; Rare variants
Descrição
Rare variants in the phospholipase D3 gene (PLD3) were associated with increased risk for late-onset Alzheimer disease (LOAD). We identified a missense mutation in PLD3 in whole-genome sequence data of a patient with autopsy confirmed Alzheimer disease (AD) and onset age of 50 years. Subsequently, we sequenced PLD3 in a Belgian early-onset Alzheimer disease (EOAD) patient (N = 261) and control (N = 319) cohort, as well as in European EOAD patients (N = 946) and control individuals (N = 1,209) ascertained in different European countries. Overall, we identified 22 rare variants with a minor allele frequency <1%, 20 missense and two splicing mutations. Burden analysis did not provide significant evidence for an enrichment of rare PLD3 variants in EOAD patients in any of the patient/control cohorts. Also, meta-analysis of the PLD3 data, including a published dataset of a German EOAD cohort, was not significant (P = 0.43; OR = 1.53, 95% CI 0.60-3.31). Consequently, our data do not support a role for PLD3 rare variants in the genetic etiology of EOAD in European EOAD patients. Our data corroborate the negative replication data obtained in LOAD studies and therefore a genetic role of PLD3 in AD remains to be demonstrated.
