Fine-Mapping of SNCA in Rapid Eye Movement Sleep Behavior Disorder and Overt Synucleinopathies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F20%3A10410069" target="_blank" >RIV/00216208:11110/20:10410069 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00064165:_____/20:10410069

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xFlkIXOn17" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=xFlkIXOn17</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/ana.25687" target="_blank" >10.1002/ana.25687</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Fine-Mapping of SNCA in Rapid Eye Movement Sleep Behavior Disorder and Overt Synucleinopathies

Popis výsledku v původním jazyce

Objective: Rapid eye movement sleep behavior disorder (RBD) is a prodromal synucleinopathy, as &gt;80% will eventually convert to overt synucleinopathy. We performed an in-depth analysis of the SNCA locus to identify RBD-specific risk variants. Methods: Full sequencing and genotyping of SNCA was performed in isolated/idiopathic RBD (iRBD, n = 1,076), Parkinson disease (PD, n = 1,013), dementia with Lewy bodies (DLB, n = 415), and control subjects (n = 6,155). The iRBD cases were diagnosed with RBD prior to neurodegeneration, although some have since converted. A replication cohort from 23andMe of PD patients with probable RBD (pRBD) was also analyzed (n = 1,782 cases; n = 131,250 controls). Adjusted logistic regression models and meta-analyses were performed. Effects on conversion rate were analyzed in 432 RBD patients with available data using Kaplan-Meier survival analysis. Results: A 5&apos;-region SNCA variant (rs10005233) was associated with iRBD (odds ratio [OR] = 1.43, p = 1.1E-08), which was replicated in pRBD. This variant is in linkage disequilibrium (LD) with other 5&apos; risk variants across the different synucleinopathies. An independent iRBD-specific suggestive association (rs11732740) was detected at the 3&apos; of SNCA (OR = 1.32, p = 4.7E-04, not statistically significant after Bonferroni correction). Homozygous carriers of both iRBD-specific SNPs were at highly increased risk for iRBD (OR = 5.74, p = 2E-06). The known top PD-associated variant (3&apos; variant rs356182) had an opposite direction of effect in iRBD compared to PD. Interpretation: There is a distinct pattern of association at the SNCA locus in RBD as compared to PD, with an opposite direction of effect at the 3&apos; of SNCA . Several 5&apos; SNCA variants are associated with iRBD and with pRBD in overt synucleinopathies.

Název v anglickém jazyce

Fine-Mapping of SNCA in Rapid Eye Movement Sleep Behavior Disorder and Overt Synucleinopathies

Popis výsledku anglicky

Objective: Rapid eye movement sleep behavior disorder (RBD) is a prodromal synucleinopathy, as &gt;80% will eventually convert to overt synucleinopathy. We performed an in-depth analysis of the SNCA locus to identify RBD-specific risk variants. Methods: Full sequencing and genotyping of SNCA was performed in isolated/idiopathic RBD (iRBD, n = 1,076), Parkinson disease (PD, n = 1,013), dementia with Lewy bodies (DLB, n = 415), and control subjects (n = 6,155). The iRBD cases were diagnosed with RBD prior to neurodegeneration, although some have since converted. A replication cohort from 23andMe of PD patients with probable RBD (pRBD) was also analyzed (n = 1,782 cases; n = 131,250 controls). Adjusted logistic regression models and meta-analyses were performed. Effects on conversion rate were analyzed in 432 RBD patients with available data using Kaplan-Meier survival analysis. Results: A 5&apos;-region SNCA variant (rs10005233) was associated with iRBD (odds ratio [OR] = 1.43, p = 1.1E-08), which was replicated in pRBD. This variant is in linkage disequilibrium (LD) with other 5&apos; risk variants across the different synucleinopathies. An independent iRBD-specific suggestive association (rs11732740) was detected at the 3&apos; of SNCA (OR = 1.32, p = 4.7E-04, not statistically significant after Bonferroni correction). Homozygous carriers of both iRBD-specific SNPs were at highly increased risk for iRBD (OR = 5.74, p = 2E-06). The known top PD-associated variant (3&apos; variant rs356182) had an opposite direction of effect in iRBD compared to PD. Interpretation: There is a distinct pattern of association at the SNCA locus in RBD as compared to PD, with an opposite direction of effect at the 3&apos; of SNCA . Several 5&apos; SNCA variants are associated with iRBD and with pRBD in overt synucleinopathies.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30103 - Neurosciences (including psychophysiology)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Annals of Neurology

ISSN

0364-5134

e-ISSN

—

Svazek periodika

87

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

15

Strana od-do

584-598

Kód UT WoS článku

000512809200001

EID výsledku v databázi Scopus

2-s2.0-85079453924