Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F15%3A%230001035" target="_blank" >RIV/00064190:_____/15:#0001035 - isvavai.cz</a>
Nalezeny alternativní kódy
RIV/00216208:11110/15:10313176 RIV/00216208:11120/15:43910452
Výsledek na webu
<a href="http://dx.doi.org/10.1002/humu.22908" target="_blank" >http://dx.doi.org/10.1002/humu.22908</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/humu.22908" target="_blank" >10.1002/humu.22908</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Rare Variants in PLD3 Do Not Affect Risk for Early-Onset Alzheimer Disease in a European Consortium Cohort
Popis výsledku anglicky
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.
Klasifikace
Druh
J<sub>x</sub> - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)
CEP obor
FH - Neurologie, neurochirurgie, neurovědy
OECD FORD obor
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Návaznosti výsledku
Projekt
<a href="/cs/project/NT12094" target="_blank" >NT12094: Multidisciplinární přístup v diagnostice frontotemporálních lobárních degenerací a tauopatií: komplexní pohled na patogenetické mechanismy</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2015
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
HUMAN MUTATION
ISSN
1059-7794
e-ISSN
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Svazek periodika
36
Číslo periodika v rámci svazku
12
Stát vydavatele periodika
US - Spojené státy americké
Počet stran výsledku
10
Strana od-do
1226-1235
Kód UT WoS článku
000364788500015
EID výsledku v databázi Scopus
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