Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.

• MeSH
• celogenomová asociační studie * MeSH
• genetická predispozice k nemoci * MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• mendelovská randomizace MeSH
• rizikové faktory MeSH
• strojové učení MeSH
• syndrom neklidných nohou * genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH

Recent studies reported association of sleep-disordered breathing (SDB) with testosterone and vitamin D deficiency. Low testosterone and vitamin D levels have been linked to fatigue and excessive daytime sleepiness (EDS). However, the impact of testosterone and vitamin D deficiency on EDS in subjects with SDB remains unknown. The aim of this study was to explore the predictors of EDS in habitual snorers. Role of testosterone, and vitamin D was studied in detail. We also looked for associations between testosterone, vitamin D, and sleep-related indices. We prospectively enrolled 291 consecutive male patients with habitual snoring. Baseline clinical characteristics were recorded on admission. Standard overnight polysomnography was performed to detect SDB, and Epworth Sleepiness Scale (ESS) was used to assess EDS. Blood samples were obtained in a fasting condition in the morning after polysomnography to determine levels of testosterone and vitamin D. Respiratory disturbance index (RDI) (95 % CI: 1.004-1.024, p=0.005) and the use of antihistamines (95 % CI: 1.083-11.901, p=0.037) were the only independent variables significantly associated with EDS in binary logistic regression analysis. In linear multiple regression analysis, body mass index (BMI) (Beta=-0.282, p<0.001) and oxygen desaturation index (Beta=-0.150, p=0.043) were the only independent variables significantly associated with testosterone levels, and BMI (Beta=-0.142, p=0.016) was the only independent variable significantly associated with vitamin D. We failed to find any independent association of testosterone and vitamin D with subjectively rated EDS among habitual snorers. Our results suggest an independent association between the magnitude of nocturnal desaturation and testosterone levels.

• MeSH
• index tělesné hmotnosti * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nedostatek vitaminu D krev   patologie   MeSH
• obstrukční spánková apnoe krev   patologie   MeSH
• polysomnografie metody   MeSH
• poruchy nadměrné spavosti krev   patologie   MeSH
• prospektivní studie MeSH
• testosteron krev   MeSH
• vitamin D krev   MeSH
• vitaminy krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Spojené království epidemiologie   MeSH
• Názvy látek
• testosteron MeSH
• vitamin D MeSH
• vitaminy MeSH

Contactless measurements during the night by a 3-D-camera are less time-consuming in comparison to polysomnography because they do not require sophisticated wiring. However, it is not clear what might be the diagnostic benefit and accuracy of this technology. We investigated 59 persons simultaneously by polysomnography and 3-D-camera and visual perceptive computing (19 patients with restless legs syndrome (RLS), 21 patients with obstructive sleep apnea (OSA), and 19 healthy volunteers). There was a significant correlation between the apnea hypopnea index (AHI) measured by polysomnography and respiratory events measured with the 3-D-camera in OSA patients (r = 0.823; p < 0.001). The receiver operating characteristic curve yielded a sensitivity of 90% for OSA with a specificity of 71.4%. In RLS patients 72.8% of leg movements confirmed by polysomnography could be detected by 3-D-video and a significant moderate correlation was found between PLM measured by polysomnography and by the 3-D-camera (RLS: r = 0.654; p = 0.004). In total, 95.4% of the sleep epochs were correctly classified by the machine learning approach, but only 32.5% of awake epochs. Further studies should investigate, if this technique might be an alternative to home sleep testing in persons with an increased pre-test probability for OSA.

• MeSH
• audiovizuální záznam MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• polysomnografie metody   MeSH
• prospektivní studie MeSH
• ROC křivka MeSH
• senioři MeSH
• senzitivita a specificita MeSH
• strojové učení MeSH
• studie případů a kontrol MeSH
• syndrom neklidných nohou diagnóza   MeSH
• syndromy spánkové apnoe diagnóza   MeSH
• zraková percepce MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. METHODS: In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15 126 cases and 95 725 controls of European ancestry. We identified common variants by fixed-effect inverse-variance meta-analysis. Significant genome-wide signals (p≤5 × 10-8) were tested for replication in an independent GWAS of 30 770 cases and 286 913 controls, followed by a joint analysis of the discovery and replication stages. We did gene annotation, pathway, and gene-set-enrichment analyses and studied the genetic correlations between restless legs syndrome and traits of interest. FINDINGS: We identified and replicated 13 new risk loci for restless legs syndrome and confirmed the previously identified six risk loci. MEIS1 was confirmed as the strongest genetic risk factor for restless legs syndrome (odds ratio 1·92, 95% CI 1·85-1·99). Gene prioritisation, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance (associated with SEMA6D), synapse formation (NTNG1), and neuronal specification (HOXB cluster family and MYT1). INTERPRETATION: Identification of new candidate genes and associated pathways will inform future functional research. Advances in understanding of the molecular mechanisms that underlie restless legs syndrome could lead to new treatment options. We focused on common variants; thus, additional studies are needed to dissect the roles of rare and structural variations. FUNDING: Deutsche Forschungsgemeinschaft, Helmholtz Zentrum München-Deutsches Forschungszentrum für Gesundheit und Umwelt, National Research Institutions, NHS Blood and Transplant, National Institute for Health Research, British Heart Foundation, European Commission, European Research Council, National Institutes of Health, National Institute of Neurological Disorders and Stroke, NIH Research Cambridge Biomedical Research Centre, and UK Medical Research Council.

• MeSH
• běloši MeSH
• celogenomová asociační studie * MeSH
• DNA vazebné proteiny genetika   MeSH
• genetická predispozice k nemoci genetika   MeSH
• GPI-vázané proteiny genetika   MeSH
• lidé MeSH
• netriny MeSH
• proteiny nervové tkáně genetika   MeSH
• semaforiny genetika   MeSH
• syndrom neklidných nohou epidemiologie   genetika   MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• GPI-vázané proteiny MeSH
• MYT1 protein, human MeSH Prohlížeč
• netriny MeSH
• NTNG1 protein, human MeSH Prohlížeč
• proteiny nervové tkáně MeSH
• Sema6d protein, mouse MeSH Prohlížeč
• semaforiny MeSH
• transkripční faktory MeSH

Sleep abnormalities are frequently found in Parkinson's disease (PD). However, it is unclear if they are present from the initial stages of PD. We thus aimed to assess sleep disturbances in newly diagnosed PD patients. We investigated 20 untreated PD patients using the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and the PD Sleep Scale (PDSS). Video-polysomnography and multiple sleep latency test (MSLT) were performed in 15 patients and 15 healthy controls. The ESS score was abnormally high in one patient, while short MSLT times were found in three other patients. The PSQI was higher (p < 0.05) and the PDSS lower (p < 0.001) in patients compared with controls. Video-polysomnography demonstrated a higher percentage of rapid eye movement sleep without atonia (RWA) in patients compared with controls (mean 28 vs. 2.9%, p < 0.001), whereas only one patient had clinically manifested rapid eye movement sleep behavior disorder (RBD). Interestingly, the occurrence of RWA correlated with the motor score (ρ = 0.65, p < 0.05). This study demonstrates that sleep disturbances emerge, in a proportion of patients, from the early stages of PD. RWA is a common finding while RBD is rarely present in early untreated PD.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Parkinsonova nemoc komplikace   MeSH
• polysomnografie MeSH
• poruchy spánku z vnitřních příčin epidemiologie   etiologie   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: Restless legs syndrome (RLS) is associated with common variants in three intronic and intergenic regions in MEIS1, BTBD9, and MAP2K5/LBXCOR1 on chromosomes 2p, 6p and 15q. METHODS: Our study investigated these variants in 649 RLS patients and 1230 controls from the Czech Republic (290 cases and 450 controls), Austria (269 cases and 611 controls) and Finland (90 cases and 169 controls). Ten single nucleotide polymorphisms (SNPs) within the three genomic regions were selected according to the results of previous genome-wide scans. Samples were genotyped using Sequenom platforms. RESULTS: We replicated associations for all loci in the combined samples set (rs2300478 in MEIS1, p = 1.26 x 10(-5), odds ratio (OR) = 1.47, rs3923809 in BTBD9, p = 4.11 x 10(-5), OR = 1.58 and rs6494696 in MAP2K5/LBXCOR1, p = 0.04764, OR = 1.27). Analysing only familial cases against all controls, all three loci were significantly associated. Using sporadic cases only, we could confirm the association only with BTBD9. CONCLUSION: Our study shows that variants in these three loci confer consistent disease risks in patients of European descent. Among the known loci, BTBD9 seems to be the most consistent in its effect on RLS across populations and is also most independent of familial clustering.

• MeSH
• dospělí MeSH
• frekvence genu MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• homeodoménové proteiny genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• korepresorové proteiny MeSH
• lidé středního věku MeSH
• lidé MeSH
• MAP kinasa-kinasa 5 genetika   MeSH
• nádorové proteiny genetika   MeSH
• odds ratio MeSH
• proteiny nervové tkáně MeSH
• represorové proteiny genetika   MeSH
• senioři MeSH
• syndrom neklidných nohou genetika   MeSH
• transkripční faktor Meis1 MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Finsko MeSH
• Rakousko MeSH
• Názvy látek
• BTBD9 protein, human MeSH Prohlížeč
• homeodoménové proteiny MeSH
• korepresorové proteiny MeSH
• MAP kinasa-kinasa 5 MeSH
• MAP2K5 protein, human MeSH Prohlížeč
• MEIS1 protein, human MeSH Prohlížeč
• nádorové proteiny MeSH
• proteiny nervové tkáně MeSH
• represorové proteiny MeSH
• SKOR1 protein, human MeSH Prohlížeč
• transkripční faktor Meis1 MeSH
• transkripční faktory MeSH