Lack of epistatic interaction of SNCA with APOE in synucleinopathies

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216208:11110/25:10506128

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Lack of epistatic interaction of SNCA with APOE in synucleinopathies

Popis výsledku v původním jazyce

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&apos;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.

Název v anglickém jazyce

Lack of epistatic interaction of SNCA with APOE in synucleinopathies

Popis výsledku anglicky

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&apos;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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Brain Communications

ISSN

2632-1297

e-ISSN

2632-1297

Svazek periodika

7

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

8

Strana od-do

fcaf455

Kód UT WoS článku

001628504400001

EID výsledku v databázi Scopus

2-s2.0-105023903435