Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: a European early-onset dementia consortium study

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064190%3A_____%2F15%3A%230001056" target="_blank" >RIV/00064190:_____/15:#0001056 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/15:10295522 RIV/00064165:_____/15:10295522 RIV/00216208:11120/15:43913285

Výsledek na webu

<a href="http://www.neurobiologyofaging.org/article/S0197-4580(15)00114-1/fulltext" target="_blank" >http://www.neurobiologyofaging.org/article/S0197-4580(15)00114-1/fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.neurobiolaging.2015.02.014" target="_blank" >10.1016/j.neurobiolaging.2015.02.014</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: a European early-onset dementia consortium study

Popis výsledku v původním jazyce

Meta-analysis of existing genome-wide association studies on Alzheimer's disease (AD) showed subgenome-wide association of an intronic variant in the sequestosome 1 (SQSTM1) gene with AD. We performed targeted resequencing of SQSTM1 in Flanders-Belgian AD patients selected to be enriched for a genetic background (n = 435) and geographically matched nonaffected individuals (n = 872) to investigate the role of both common and rare SQSTM1 variants. Results were extended to the European earlyonset dementia cohorts (926 early-onset Alzheimer's disease [EOAD] patients and 1476 nonaffected individuals). Of the 61 detected exonic variants in SQSTM1, the majority were rare (n = 57). Rare variant (minor allele frequency <0.01) burden analysis did not reveal an increased frequency of rare variants in EOAD patients in any of the separate study populations nor when meta-analyzing all cohorts. Common variants p.D292- and p.R312- showed nominal association with AD (odds ratio(p.D292=) - 1.11 [95% confidence interval = 1-1.22], p = 0.04), only when including the Flanders-Belgian cohort in the meta-analysis. We cannot exclude a role of SQSTM1 genetic variability in late-onset AD, but our data indicate that SQSTM1 does not play a major role in the etiology of EOAD.

Název v anglickém jazyce

Genetic variability in SQSTM1 and risk of early-onset Alzheimer dementia: a European early-onset dementia consortium study

Popis výsledku anglicky

Meta-analysis of existing genome-wide association studies on Alzheimer's disease (AD) showed subgenome-wide association of an intronic variant in the sequestosome 1 (SQSTM1) gene with AD. We performed targeted resequencing of SQSTM1 in Flanders-Belgian AD patients selected to be enriched for a genetic background (n = 435) and geographically matched nonaffected individuals (n = 872) to investigate the role of both common and rare SQSTM1 variants. Results were extended to the European earlyonset dementia cohorts (926 early-onset Alzheimer's disease [EOAD] patients and 1476 nonaffected individuals). Of the 61 detected exonic variants in SQSTM1, the majority were rare (n = 57). Rare variant (minor allele frequency <0.01) burden analysis did not reveal an increased frequency of rare variants in EOAD patients in any of the separate study populations nor when meta-analyzing all cohorts. Common variants p.D292- and p.R312- showed nominal association with AD (odds ratio(p.D292=) - 1.11 [95% confidence interval = 1-1.22], p = 0.04), only when including the Flanders-Belgian cohort in the meta-analysis. We cannot exclude a role of SQSTM1 genetic variability in late-onset AD, but our data indicate that SQSTM1 does not play a major role in the etiology of EOAD.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FH - Neurologie, neurochirurgie, neurovědy

OECD FORD obor

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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)

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

NEUROBIOLOGY OF AGING

ISSN

0197-4580

e-ISSN

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Svazek periodika

36

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

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Kód UT WoS článku

000355100900025

EID výsledku v databázi Scopus

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