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Risk variants of the ?-synuclein locus and REM sleep behavior disorder in Parkinson's disease: a genetic association study.

ABSTRACT: Parkinson's disease is a heterogeneous disorder where genetic factors may underlie clinical variability. Rapid eye movement sleep behavior disorder (RBD) is a parasomnia strongly linked to synucleinopathies, including Parkinson's disease. We hypothesized that SNCA variants conferring risk of Parkinson's disease would also predispose to an RBD phenotype.We assessed possible RBD (pRBD) status using the RBD screening questionnaire and investigated known susceptibility variants for Parkinson's disease located in the ?-synuclein (SNCA) and tau (MAPT) gene loci in 325 Parkinson's disease patients. Associations between genetic risk variants and RBD were investigated by logistic regression, and an independent dataset of 382 patients from the Parkinson's Progression Marker Initiative (PPMI) study was used for replication.pRBD was associated with rs3756063 located in the 5' region of SNCA (two-sided p?=?0.018, odds ratio 1.44). We replicated this finding in the PPMI dataset (one-sided p?=?0.036, odds ratio 1.35) and meta-analyzed the results (two-sided p?=?0.0032, odds ratio 1.40). The Parkinson's disease risk variant in the 3' region of SNCA and the MAPT variant showed no association with pRBD.Our findings provide proof of principle that a largely stable, dichotomous clinical feature of Parkinson's disease can be linked to a specific genetic susceptibility profile. Indirectly, it also supports the hypothesis of RBD as relevant marker for a distinct subtype of the disorder.

SUBMITTER: Bjornara KA

PROVIDER: S-EPMC5822630 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Risk variants of the α-synuclein locus and REM sleep behavior disorder in Parkinson's disease: a genetic association study.

Bjørnarå Kari Anne KA Pihlstrøm Lasse L Dietrichs Espen E Toft Mathias M

BMC neurology 20180221 1

<h4>Background</h4>Parkinson's disease is a heterogeneous disorder where genetic factors may underlie clinical variability. Rapid eye movement sleep behavior disorder (RBD) is a parasomnia strongly linked to synucleinopathies, including Parkinson's disease. We hypothesized that SNCA variants conferring risk of Parkinson's disease would also predispose to an RBD phenotype.<h4>Methods</h4>We assessed possible RBD (pRBD) status using the RBD screening questionnaire and investigated known susceptibi ...[more]

PMID: 29466944

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Project description:ObjectivesTo develop a polysomnographic video-based scale for rating the severity of REM sleep behavior disorder (RBD), to classify the severity of RBD and to determine the intraindividual variability of RBD in patients with Parkinson disease (PD).MethodsTwenty PD patients identified with RBD were investigated with video-supported polysomnography (PSG). Seventy-three motor behavior events during REM sleep were graded visually and polysomnographically on an event-to-event basis according to categorical location of movements: "0" = no visible movement; "1" = slight movements or jerks "2" = movements involving proximal extremities, including violent behavior; "3" = axial involvement including bed falls. Vocalizations were rated as "1" for present or "0" for absent. Ratings were performed by 2 blinded raters. Reliability was calculated with Cohen's ?. Final RBD severity was determined by the highest score given. This rating scale was then used to compare RBD severity and density, calculated as RBD episodes per REM sleep minute over 2 consecutive nights in 10 additional PD patients with RBD. Statistical significance was determined by effect size (Hedges' g) and calculation of the confidence interval.ResultsInterrater reliability of the scale was 0.8 for movement data and 0.89 for vocalization data. Intraindividual RBD density varied significantly (effect size 0.5 ± 0.22; confidence interval 0.2 to 0.79) by factor 2.5 between the 2 PSG nights. Final RBD severity score differed in 60% of patients between nights 1 and 2. Forty percent of patients showed violent behavior, but only on one night. All patients had severely disturbed sleep with reduced sleep efficiency, loss of slow wave sleep, sleep fragmentation, and an increased periodic limb movement (PLM) index.ConclusionThe RBD severity scale (RBDSS) is a reliable, easy-to-use tool for assessing motor events during REM sleep with PSG. Severity and phenomenology of RBD shows a significant variability in the individual PD patient.

Dataset Information

Risk variants of the ?-synuclein locus and REM sleep behavior disorder in Parkinson's disease: a genetic association study.

Publications

Risk variants of the α-synuclein locus and REM sleep behavior disorder in Parkinson's disease: a genetic association study.

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