Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F18%3A10376306" target="_blank" >RIV/00216208:11110/18:10376306 - isvavai.cz</a>
Alternative codes found
RIV/00064190:_____/18:N0000035
Result on the web
<a href="https://doi.org/10.1016/j.neurobiolaging.2017.10.012" target="_blank" >https://doi.org/10.1016/j.neurobiolaging.2017.10.012</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.neurobiolaging.2017.10.012" target="_blank" >10.1016/j.neurobiolaging.2017.10.012</a>
Alternative languages
Result language
angličtina
Original language name
Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort
Original language description
TANK-binding kinase 1 (TBK1) loss-of-function (LoF) mutations are known to cause frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS), often combined with memory deficits early in the disease course. We performed targeted resequencing of TBK1 in 1253 early onset Alzheimer's disease (EOAD) patients from 8 European countries to investigate whether pathogenic TBK1 mutations are enriched among patients with clinical diagnosis of EOAD. Variant frequencies were compared against 2117 origin-matched controls. We identified only 1 LoF mutation (p.Thr79del) in a patient clinically diagnosed with Alzheimer's disease and a positive family history of ALS. We did not observe enrichment of rare variants in EOAD patients compared to controls, nor of rare variants affecting NFκB induction. Of 3 common coding variants, rs7486100 showed evidence of association (OR 1.46 [95% CI 1.13-1.9]; p-value 0.01). Homozygous carriers of the risk allele showed reduced expression of TBK1 (p-value 0.03). Our findings are not indicative of a significant role for TBK1 mutations in EOAD. The association between common variants in TBK1, disease risk and reduced TBK1 expression warrants follow-up in FTD/ALS cohorts.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30109 - Pathology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Neurobiology of Aging
ISSN
0197-4580
e-ISSN
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Volume of the periodical
62
Issue of the periodical within the volume
February
Country of publishing house
GB - UNITED KINGDOM
Number of pages
7
Pages from-to
"245e1"-"245e7"
UT code for WoS article
000418478600027
EID of the result in the Scopus database
2-s2.0-85035129689