Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort
Cacace, Rita (University of Antwerp)
Van den Bossche, Tobi (University Hospital Antwerp (Bèlgica))
Engelborghs, Sebastiaan (University Hospital Antwerp (Bèlgica))
Geerts, Nathalie (University of Antwerp)
Laureys, Annelies (University of Antwerp)
Dillen, Lubina (University of Antwerp)
Graff, Caroline (Karolinska University Hospital and Karolinska Institutet (Suècia))
Thonberg, Håkan (Karolinska University Hospital and Karolinska Institutet (Suècia))
Chiang, Huei-Hsin (Karolinska University Hospital and Karolinska Institutet (Suècia))
Pastor, Pau (Instituto de Salud Carlos III)
Ortega-Cubero, Sara (Instituto de Salud Carlos III)
Pastor, Maria A. (Universidad de Navarra. Facultad de Medicina)
Diehl-Schmid, Janine (Technische Universität München)
Alexopoulos, Panagiotis (Technische Universität München)
Benussi, Luisa (Istituto Centro San Giovanni di Dio-Fatebenefratelli)
Ghidoni, Roberta (Istituto Centro San Giovanni di Dio-Fatebenefratelli)
Binetti, Giuliano (Istituto Centro San Giovanni di Dio-Fatebenefratelli)
Nacmias, Benedetta (University of Florence)
Sorbi, Sandro (University of Florence)
Sanchez-Valle, Raquel (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Llado Plarrumani, Albert (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Gelpi, Ellen (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Almeida, Maria Rosário (University of Coimbra)
Santana, Isabel (University of Coimbra)
Tsolaki, Magda (Aristotle University of Thessaloniki)
Koutroumani, Maria (Aristotle University of Thessaloniki)
Clarimón, Jordi (Universitat Autònoma de Barcelona)
Lleó Bisa, Alberto (Universitat Autònoma de Barcelona)
Fortea, Juan (Universitat Autònoma de Barcelona)
de Mendonça, Alexandre (University of Lisbon)
Martins, Madalena (University of Lisbon)
Borroni, Barbara (University of Brescia)
Padovani, Alessandro (University of Brescia)
Matej, Radoslav (Thomayer Hospital in Prague)
Rohan, Zdenek (Third Medical Faculty of Charles University in Prague)
Vandenbulcke, Mathieu (University of Leuven)
Vandenberghe, Rik (University Hospitals Leuven (Bèlgica))
De Deyn, Peter Paul (University Hospital Antwerp (Bèlgica))
Cras, Patrick (University Hospital Antwerp (Bèlgica))
van der Zee, Julie (University of Antwerp)
Sleegers, Kristel (University of Antwerp)
Van Broeckhoven, Christine (University of Antwerp)

Fecha:	2015
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Alzheimer dementia ; EOAD ; PLD3 ; Next-generation sequencing ; Rare variants ; Meta-analysis
Publicado en:	Human mutation, Vol. 36 (october 2015) , p. 1226-1235, ISSN 1098-1004

DOI: 10.1002/humu.22908
PMID: 26411346

10 p, 498.4 KB

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