Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohort
| Main Author: | |
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| Publication Date: | 2015 |
| Other Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) |
| Download full: | http://hdl.handle.net/10451/53458 |
Summary: | © 2015 The Authors. ∗∗ Human Mutation published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
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Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohortAlzheimer dementiaEOADPLD3Meta-analysisNext-generation sequencingRare variants© 2015 The Authors. ∗∗ Human Mutation published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.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.MetLife Foundation for Medical Research Award (USA); the U.S. Army Medical Research and Material Command (USAMRMC) Research Award; the Janssen Pharmaceutical Stellar Research Project; the Belgian Science Policy Office Interuniversity Attraction Poles program; the Alzheimer Research Foundation (SAO-FRA); the Flemish Government initiated Flanders Impulse Program on Networks for Dementia Research (VIND); the Flemish Government initiated Methusalem Excellence Program; the Research Foundation Flanders (FWO); the University of Antwerp Research Fund; ISCIII, Cofinancia Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, Otra manera de hacer Europa (PI11/00234); Instituto de Salud Carlos III (PI12/01311); Grant Agency of Ministry of Health and Charles University Project PRVOUK P26/1/4 (IGA NT12094-5); the Fundação para a Ciência e a Tecnologia (SFRH/BPD/29354/2006); the Ricerca Corrente, Italian Ministry of Health; the Cassa di Risparmio di Pistoia e Pescia (2014.0365); the Cassa di Risparmio di Firenze (2014.0310); Ministry of Health (RF-2010-2319722); Swedish Brain Power, Swedish Research Council (521-2010-3134, A031340); the King Gustaf V and Queen Victoria's Foundation of Freemasons; the Foundations of Marianne and Marcus Wallenberg, Knut and Alice Wallenberg, Gun and Bertil Stohne, Gamla tjänarinnor, Demensfonden Swedish Alzheimer Foundation (462081); StratNeuro at Karolinska Institute (KI).WileyRepositório da Universidade de LisboaCacace, RitaVan den Bossche, TobiEngelborghs, SebastiaanGeerts, NathalieLaureys, AnneliesDillen, LubinaGraff, CarolineThonberg, HåkanChiang, Huei-HsinPastor, PauOrtega-Cubero, SaraPastor, Maria A.Diehl-Schmid, JanineAlexopoulos, PanagiotisBenussi, LuisaGhidoni, RobertaBinetti, GiulianoNacmias, BenedettaSorbi, SandroSanchez-Valle, RaquelLladó, AlbertGelpi, EllenAlmeida, Maria RosárioSantana, IsabelTsolaki, MagdaKoutroumani, MariaClarimon, JordiLleó, AlbertoFortea, JuanDe Mendonça, AlexandreMartins, MadalenaBorroni, BarbaraPadovani, AlessandroMatej, RadoslavRohan, ZdenekVandenbulcke, MathieuVandenberghe, RikDe Deyn, Peter P.Cras, Patrickvan der Zee, JulieSleegers, KristelVan Broeckhoven, Christine2022-06-23T16:10:28Z20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/53458engHum Mutat. 2015 Dec;36(12):1226-12351059-779410.1002/humu.229081098-1004info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-03-17T14:46:50Zoai:repositorio.ulisboa.pt:10451/53458Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-29T03:24:22.371424Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse |
| dc.title.none.fl_str_mv |
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohort |
| title |
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohort |
| spellingShingle |
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohort Cacace, Rita Alzheimer dementia EOAD PLD3 Meta-analysis Next-generation sequencing Rare variants |
| title_short |
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohort |
| title_full |
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohort |
| title_fullStr |
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohort |
| title_full_unstemmed |
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohort |
| title_sort |
Rare variants in PLD3 do not affect risk for early-onset Alzheimer disease in a european consortium cohort |
| author |
Cacace, Rita |
| author_facet |
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 |
| author_role |
author |
| author2 |
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 |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
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 |
| dc.subject.por.fl_str_mv |
Alzheimer dementia EOAD PLD3 Meta-analysis Next-generation sequencing Rare variants |
| topic |
Alzheimer dementia EOAD PLD3 Meta-analysis Next-generation sequencing Rare variants |
| description |
© 2015 The Authors. ∗∗ Human Mutation published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
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2015 |
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2015 2015-01-01T00:00:00Z 2022-06-23T16:10:28Z |
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eng |
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Hum Mutat. 2015 Dec;36(12):1226-1235 1059-7794 10.1002/humu.22908 1098-1004 |
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