Lack of epistatic interaction of SNCA with APOE in synucleinopathies
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064165%3A_____%2F25%3A10506128" target="_blank" >RIV/00064165:_____/25:10506128 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/25:10506128
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=zKEERwdeoc" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=zKEERwdeoc</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/braincomms/fcaf455" target="_blank" >10.1093/braincomms/fcaf455</a>
Alternative languages
Result language
angličtina
Original language name
Lack of epistatic interaction of SNCA with APOE in synucleinopathies
Original language description
Two recent studies suggested that the APOE epsilon 4 haplotype was associated with increased alpha-synuclein pathology in cell and mouse models. Genetic variants in the SNCA region have strong association with Parkinson's disease (PD), dementia with Lewy bodies (DLB) and idiopathic REM sleep behaviour disorder (iRBD), while APOE is a genetic risk determinant for only DLB. To determine if genetic-level interactions between SNCA and APOE exists that can explain the protein-level association, we investigated the genotypic interaction of APOE and SNCA in cohorts of PD, DLB and iRBD. We analysed genome-wide association study (GWAS) data from 5229 PD patients and 5480 controls, 2610 DLB patients and 1920 controls, and 1055 iRBD patients and 3667 controls. We used logistic regression interaction models across all three cohorts independently between the (i) top GWAS signals of SNCA single nucleotide polymorphisms (SNPs) and APOE haplotypes and (ii) SNPxSNP and three-way SNP interaction across the entire coding region plus 200 kb flanking each gene. No significant interactions were found to be associated with any of the synucleinopathies after correction for multiple testing. Our results do not support a role for genetic interactions between APOE and SNCA across PD, DLB and iRBD. Since the tested genetic variants affect the expression and function of these proteins, it is likely that any interactions between them do not affect the risk of PD, DLB and iRBD. Saini et al. report no evidence of genetic interaction between SNCA and APOE in 8855 synucleinopathy patients and 11 067 controls. The authors found no evidence of genetic epistasis between these genes, suggesting that protein-level interactions between APOE and SNCA are unlikely to be driven by synucleinopathy risk variants.
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
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
—
Continuities
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Brain Communications
ISSN
2632-1297
e-ISSN
2632-1297
Volume of the periodical
7
Issue of the periodical within the volume
6
Country of publishing house
GB - UNITED KINGDOM
Number of pages
8
Pages from-to
fcaf455
UT code for WoS article
001628504400001
EID of the result in the Scopus database
2-s2.0-105023903435