Trenkwalder, Claudia

[["dc.bibliographiccitation.artnumber","e98092"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Schulte, Eva C."],["dc.contributor.author","Schramm, Katharina"],["dc.contributor.author","Schurmann, Claudia"],["dc.contributor.author","Lichtner, Peter"],["dc.contributor.author","Herder, Christian"],["dc.contributor.author","Roden, Michael"],["dc.contributor.author","Gieger, Christian"],["dc.contributor.author","Peters, Annette"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Hoegl, Birgit"],["dc.contributor.author","Frauscher, Birgit"],["dc.contributor.author","Berger, Klaus"],["dc.contributor.author","Fietze, Ingo"],["dc.contributor.author","Gross, Nadine"],["dc.contributor.author","Stiasny-Kolster, Karin"],["dc.contributor.author","Oertel, Wolfgang"],["dc.contributor.author","Bachmann, Cornelius G."],["dc.contributor.author","Paulus, Walter J."],["dc.contributor.author","Zimprich, Alexander"],["dc.contributor.author","Voelzke, Henry"],["dc.contributor.author","Schminke, Ulf"],["dc.contributor.author","Nauck, Matthias"],["dc.contributor.author","Illig, Thomas"],["dc.contributor.author","Meitinger, Thomas"],["dc.contributor.author","Mueller-Myhsok, Bertram"],["dc.contributor.author","Prokisch, Holger"],["dc.contributor.author","Winkelmann, Juliane"],["dc.date.accessioned","2018-11-07T09:39:56Z"],["dc.date.available","2018-11-07T09:39:56Z"],["dc.date.issued","2014"],["dc.description.abstract","Restless legs syndrome (RLS) is a common neurologic disorder characterized by nightly dysesthesias affecting the legs primarily during periods of rest and relieved by movement. RLS is a complex genetic disease and susceptibility factors in six genomic regions have been identified by means of genome-wide association studies (GWAS). For some complex genetic traits, expression quantitative trait loci (eQTLs) are enriched among trait-associated single nucleotide polymorphisms (SNPs). With the aim of identifying new genetic susceptibility factors for RLS, we assessed the 332 best-associated SNPs from the genome-wide phase of the to date largest RLS GWAS for cis-eQTL effects in peripheral blood from individuals of European descent. In 740 individuals belonging to the KORA general population cohort, 52 cis-eQTLs with p(nominal) < 10(-3) were identified, while in 976 individuals belonging to the SHIP-TREND general population study 53 cis-eQTLs with p(nominal) < 10(-3) were present. 23 of these cis-eQTLs overlapped between the two cohorts. Subsequently, the twelve of the 23 cis-eQTL SNPs, which were not located at an already published RLS-associated locus, were tested for association in 2449 RLS cases and 1462 controls. The top SNP, located in the DET1 gene, was nominally significant (p < 0.05) but did not withstand correction for multiple testing (p = 0.42). Although a similar approach has been used successfully with regard to other complex diseases, we were unable to identify new genetic susceptibility factor for RLS by adding this novel level of functional assessment to RLS GWAS data."],["dc.identifier.doi","10.1371/journal.pone.0098092"],["dc.identifier.isi","000336790800023"],["dc.identifier.pmid","24875634"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10183"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33404"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Blood cis-eQTL Analysis Fails to Identify Novel Association Signals among Sub-Threshold Candidates from Genome-Wide Association Studies in Restless Legs Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","85"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The American Journal of Human Genetics"],["dc.bibliographiccitation.lastpage","95"],["dc.bibliographiccitation.volume","95"],["dc.contributor.author","Schulte, Eva C."],["dc.contributor.author","Kousi, Maria"],["dc.contributor.author","Tan, Perciliz L."],["dc.contributor.author","Tilch, Erik"],["dc.contributor.author","Knauf, Franziska"],["dc.contributor.author","Lichtner, Peter"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Hoegl, Birgit"],["dc.contributor.author","Frauscher, Birgit"],["dc.contributor.author","Berger, Klaus"],["dc.contributor.author","Fietze, Ingo"],["dc.contributor.author","Hornyak, Magdolna"],["dc.contributor.author","Oertel, Wolfgang Hermann"],["dc.contributor.author","Bachmann, Cornelius G."],["dc.contributor.author","Zimprich, Alexander"],["dc.contributor.author","Peters, Annette"],["dc.contributor.author","Gieger, Christian"],["dc.contributor.author","Meitinger, Thomas"],["dc.contributor.author","Mueller-Myhsok, Bertram"],["dc.contributor.author","Katsanis, Nicholas"],["dc.contributor.author","Winkelmann, Juliane"],["dc.date.accessioned","2018-11-07T09:37:42Z"],["dc.date.available","2018-11-07T09:37:42Z"],["dc.date.issued","2014"],["dc.description.abstract","Restless legs syndrome (RLS) is a common neurologic condition characterized by nocturnal dysesthesias and an urge to move, affecting the legs. RLS is a complex trait, for which genome-wide association studies (GWASs) have identified common susceptibility alleles of modest (OR 1.2-1.7) risk at six genomic loci. Among these, variants in MEIS1 have emerged as the largest risk factors for RLS, suggesting that perturbations in this transcription factor might be causally related to RLS susceptibility. To establish this causality, direction of effect, and total genetic burden of MEIS1, we interrogated 188 case subjects and 182 control subjects for rare alleles not captured by previous GWASs, followed by genotyping of similar to 3,000 case subjects and 3,000 control subjects, and concluded with systematic functionalization of all discovered variants using a previously established in vivo model of neurogenesis. We observed a significant excess of rare MEIS1 variants in individuals with RLS. Subsequent assessment of all nonsynonymous variants by in vivo complementation revealed an excess of loss-of-function alleles in individuals with RLS. Strikingly, these alleles compromised the function of the canonical MEIS1 splice isoform but were irrelevant to an isoform known to utilize an alternative 3' sequence. Our data link MEIS1 loss of function to the etiopathology of RLS, highlight how combined sequencing and systematic functional annotation of rare variation at GWAS loci can detect risk burden, and offer a plausible explanation for the specificity of phenotypic expressivity of loss-of-function alleles at a locus broadly necessary for neurogenesis and neurodevelopment."],["dc.identifier.doi","10.1016/j.ajhg.2014.06.005"],["dc.identifier.isi","000338904100007"],["dc.identifier.pmid","24995868"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11537"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32900"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","1537-6605"],["dc.relation.issn","0002-9297"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/3.0"],["dc.title","Targeted Resequencing and Systematic In Vivo Functional Testing Identifies Rare Variants in MEIS1 as Significant Contributors to Restless Legs Syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1478"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Movement Disorders"],["dc.bibliographiccitation.lastpage","1482"],["dc.bibliographiccitation.volume","32"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Winkelmann, Juliane"],["dc.contributor.author","Oertel, Wolfgang H."],["dc.contributor.author","Virgin, Garth"],["dc.contributor.author","Roubert, Bernard"],["dc.contributor.author","Mezzacasa, Anna"],["dc.date.accessioned","2018-10-10T06:59:42Z"],["dc.date.available","2018-10-10T06:59:42Z"],["dc.date.issued","2017-10"],["dc.description.abstract","Compromised iron status is important in restless legs syndrome pathophysiology. We compared the efficacy and tolerability of ferric carboxymaltose (single intravenous dose) versus placebo for restless legs syndrome treatment in iron-deficient nonanemic patients."],["dc.fs.pkfprnr","47312"],["dc.identifier.doi","10.1002/mds.27040"],["dc.identifier.fs","634109"],["dc.identifier.pmid","28643901"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16381"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15916"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1531-8257"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e82879"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Zech, Michael"],["dc.contributor.author","Nuebling, Georg"],["dc.contributor.author","Castrop, Florian"],["dc.contributor.author","Jochim, Angela"],["dc.contributor.author","Schulte, Eva C."],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Lichtner, Peter"],["dc.contributor.author","Peters, Annette"],["dc.contributor.author","Gieger, Christian"],["dc.contributor.author","Marquardt, Thorsten"],["dc.contributor.author","Vanier, Marie T."],["dc.contributor.author","Latour, Philippe"],["dc.contributor.author","Kluenemann, Hans H."],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Diehlschmid, Janine"],["dc.contributor.author","Perneczky, Robert"],["dc.contributor.author","Meitinger, Thomas"],["dc.contributor.author","Oexle, Konrad"],["dc.contributor.author","Haslinger, Bernhard"],["dc.contributor.author","Lorenzl, Stefan"],["dc.contributor.author","Winkelmann, Juliane"],["dc.date.accessioned","2018-11-07T09:16:25Z"],["dc.date.available","2018-11-07T09:16:25Z"],["dc.date.issued","2013"],["dc.description.abstract","Niemann-Pick type C (NPC) disease is a rare autosomal-recessively inherited lysosomal storage disorder caused by mutations in NPC1 (95%) or NPC2. Given the highly variable phenotype, diagnosis is challenging and particularly late-onset forms with predominantly neuropsychiatric presentations are likely underdiagnosed. Pathophysiologically, genetic alterations compromising the endosomal/lysosomal system are linked with age-related neurodegenerative disorders. We sought to examine a possible association of rare sequence variants in NPC1 and NPC2 with Parkinson's disease (PD), frontotemporal lobar degeneration (FTLD) and progressive supranuclear palsy (PSP), and to genetically determine the proportion of potentially misdiagnosed NPC patients in these neurodegenerative conditions. By means of high-resolution melting, we screened the coding regions of NPC1 and NPC2 for rare genetic variation in a homogenous German sample of patients clinically diagnosed with PD (n = 563), FTLD (n = 133) and PSP (n = 94), and 846 population-based controls. The frequencies of rare sequence variants in NPC1/2 did not differ significantly between patients and controls. Disease-associated NPC1/2 mutations were found in six PD patients (1.1%) and seven control subjects (0.8%), but not in FTLD or PSP. All rare variation was detected in the heterozygous state and no compound heterozygotes were observed. Our data do not support the hypothesis that rare NPC1/2 variants confer susceptibility for PD, FTLD, or PSP in the German population. Misdiagnosed NPC patients were not present in our samples. However, further assessment of NPC disease genes in age-related neurodegeneration is warranted."],["dc.identifier.doi","10.1371/journal.pone.0082879"],["dc.identifier.isi","000329194700015"],["dc.identifier.pmid","24386122"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9578"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/27931"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Niemann-Pick C Disease Gene Mutations and Age-Related Neurodegenerative Disorders"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1002171"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS Genetics"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Winkelmann, Juliane"],["dc.contributor.author","Czamara, Darina"],["dc.contributor.author","Schormair, Barbara"],["dc.contributor.author","Knauf, Franziska"],["dc.contributor.author","Schulte, Eva C."],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Dauvilliers, Yves"],["dc.contributor.author","Polo, Olli"],["dc.contributor.author","Hoegl, Birgit"],["dc.contributor.author","Berger, Klaus"],["dc.contributor.author","Fuhs, Andrea"],["dc.contributor.author","Gross, Nadine"],["dc.contributor.author","Stiasny-Kolster, Karin"],["dc.contributor.author","Oertel, Wolfgang"],["dc.contributor.author","Bachmann, Cornelius G."],["dc.contributor.author","Paulus, Walter J."],["dc.contributor.author","Xiong, Lan"],["dc.contributor.author","Montplaisir, Jacques"],["dc.contributor.author","Rouleau, Guy A."],["dc.contributor.author","Fietze, Ingo"],["dc.contributor.author","Vavrova, Jana"],["dc.contributor.author","Kemlink, David"],["dc.contributor.author","Sonka, Karel"],["dc.contributor.author","Nevsimalova, Sona"],["dc.contributor.author","Lin, Siong-Chi"],["dc.contributor.author","Wszolek, Zbigniew"],["dc.contributor.author","Vilarino-Gueell, Carles"],["dc.contributor.author","Farrer, Matthew J."],["dc.contributor.author","Gschliesser, Viola"],["dc.contributor.author","Frauscher, Birgit"],["dc.contributor.author","Falkenstetter, Tina"],["dc.contributor.author","Poewe, Werner"],["dc.contributor.author","Allen, Richard P."],["dc.contributor.author","Earley, Christopher J."],["dc.contributor.author","Ondo, William G."],["dc.contributor.author","Le, Wei-Dong"],["dc.contributor.author","Spieler, Derek"],["dc.contributor.author","Kaffe, Maria"],["dc.contributor.author","Zimprich, Alexander"],["dc.contributor.author","Kettunen, Johannes"],["dc.contributor.author","Perola, Markus"],["dc.contributor.author","Silander, Kaisa"],["dc.contributor.author","Cournu-Rebeix, Isabelle"],["dc.contributor.author","Francavilla, Marcella"],["dc.contributor.author","Fontenille, Claire"],["dc.contributor.author","Fontaine, Bertrand"],["dc.contributor.author","Vodicka, Pavel"],["dc.contributor.author","Prokisch, Holger"],["dc.contributor.author","Lichtner, Peter"],["dc.contributor.author","Peppard, Paul"],["dc.contributor.author","Faraco, Juliette"],["dc.contributor.author","Mignot, Emmanuel"],["dc.contributor.author","Gieger, Christian"],["dc.contributor.author","Illig, Thomas"],["dc.contributor.author","Wichmann, Heinz-Erich"],["dc.contributor.author","Mueller-Myhsok, Bertram"],["dc.contributor.author","Meitinger, Thomas"],["dc.date.accessioned","2018-11-07T08:54:32Z"],["dc.date.available","2018-11-07T08:54:32Z"],["dc.date.issued","2011"],["dc.description.abstract","Restless legs syndrome (RLS) is a sensorimotor disorder with an age-dependent prevalence of up to 10% in the general population above 65 years of age. Affected individuals suffer from uncomfortable sensations and an urge to move in the lower limbs that occurs mainly in resting situations during the evening or at night. Moving the legs or walking leads to an improvement of symptoms. Concomitantly, patients report sleep disturbances with consequences such as reduced daytime functioning. We conducted a genome-wide association study (GWA) for RLS in 922 cases and 1,526 controls (using 301,406 SNPs) followed by a replication of 76 candidate SNPs in 3,935 cases and 5,754 controls, all of European ancestry. Herein, we identified six RLS susceptibility loci of genome-wide significance, two of them novel: an intergenic region on chromosome 2p14 (rs6747972, P = 9.03 x 10(-11), OR = 1.23) and a locus on 16q12.1 (rs3104767, P = 9.4 x 10(-19), OR = 1.35) in a linkage disequilibrium block of 140 kb containing the 59-end of TOX3 and the adjacent non-coding RNA BC034767."],["dc.identifier.doi","10.1371/journal.pgen.1002171"],["dc.identifier.isi","000293338600020"],["dc.identifier.pmid","21779176"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8169"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/22694"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1553-7404"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Genome-Wide Association Study Identifies Novel Restless Legs Syndrome Susceptibility Loci on 2p14 and 16q12.1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","49"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neurogenetics"],["dc.bibliographiccitation.lastpage","57"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Schulte, Eva C."],["dc.contributor.author","Ellwanger, Daniel C."],["dc.contributor.author","Dihanich, Sybille"],["dc.contributor.author","Manzoni, Claudia"],["dc.contributor.author","Stangl, Katrin"],["dc.contributor.author","Schormair, Barbara"],["dc.contributor.author","Graf, Elisabeth"],["dc.contributor.author","Eck, Sebastian H."],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Haubenberger, Dietrich"],["dc.contributor.author","Pirker, Walter"],["dc.contributor.author","Zimprich, Alexander"],["dc.contributor.author","Bruecke, Thomas"],["dc.contributor.author","Lichtner, Peter"],["dc.contributor.author","Peters, Annette"],["dc.contributor.author","Gieger, Christian"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Mewes, Hans-Werner"],["dc.contributor.author","Meitinger, Thomas"],["dc.contributor.author","Lewis, Patrick A."],["dc.contributor.author","Kluenemann, Hans H."],["dc.contributor.author","Winkelmann, Juliane"],["dc.date.accessioned","2018-11-07T09:43:05Z"],["dc.date.available","2018-11-07T09:43:05Z"],["dc.date.issued","2014"],["dc.description.abstract","Approximately 20 % of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset PD to identify 15 potentially causal variants. Segregation analysis and frequency assessment in 862 PD cases and 1,014 ethnically matched controls highlighted variants in EEF1D and LRRK1 as the best candidates. Mutation screening of the coding regions of these genes in 862 cases and 1,014 controls revealed several novel non-synonymous variants in both genes in cases and controls. An in silico multi-model bioinformatics analysis was used to prioritize identified variants in LRRK1 for functional follow-up. However, protein expression, subcellular localization, and cell viability were not affected by the identified variants. Although it has yet to be proven conclusively that variants in LRRK1 are indeed causative of PD, our data strengthen a possible role for LRRK1 in addition to LRRK2 in the genetic underpinnings of PD but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance."],["dc.identifier.doi","10.1007/s10048-013-0383-8"],["dc.identifier.fs","603792"],["dc.identifier.isi","000333707900007"],["dc.identifier.pmid","24241507"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10235"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34101"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1364-6753"],["dc.relation.issn","1364-6745"],["dc.rights","Goescholar"],["dc.rights.access","openAccess"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Rare variants in LRRK1 and Parkinson's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","184"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","193"],["dc.bibliographiccitation.volume","87"],["dc.contributor.author","Tilch, Erik"],["dc.contributor.author","Schormair, Barbara"],["dc.contributor.author","Zhao, Chen"],["dc.contributor.author","Salminen, Aaro V."],["dc.contributor.author","Antic Nikolic, Ana"],["dc.contributor.author","Holzknecht, Evi"],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Poewe, Werner"],["dc.contributor.author","Bachmann, Cornelius G."],["dc.contributor.author","Paulus, Walter"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Oertel, Wolfgang H."],["dc.contributor.author","Hornyak, Magdolna"],["dc.contributor.author","Fietze, Ingo"],["dc.contributor.author","Berger, Klaus"],["dc.contributor.author","Lichtner, Peter"],["dc.contributor.author","Gieger, Christian"],["dc.contributor.author","Peters, Annette"],["dc.contributor.author","Müller‐Myhsok, Bertram"],["dc.contributor.author","Hoischen, Alexander"],["dc.contributor.author","Winkelmann, Juliane"],["dc.contributor.author","Oexle, Konrad"],["dc.date.accessioned","2020-01-14T08:34:05Z"],["dc.date.accessioned","2021-10-27T13:22:02Z"],["dc.date.available","2020-01-14T08:34:05Z"],["dc.date.available","2021-10-27T13:22:02Z"],["dc.date.issued","2019"],["dc.description.abstract","OBJECTIVE: Restless legs syndrome is a frequent neurological disorder with substantial burden on individual well-being and public health. Genetic risk loci have been identified, but the causatives genes at these loci are largely unknown, so that functional investigation and clinical translation of molecular research data are still inhibited. To identify putatively causative genes, we searched for highly significant mutational burden in candidate genes. METHODS: We analyzed 84 candidate genes in 4,649 patients and 4,982 controls by next generation sequencing using molecular inversion probes that targeted mainly coding regions. The burden of low-frequency and rare variants was assessed, and in addition, an algorithm (binomial performance deviation analysis) was established to estimate independently the sequence variation in the probe binding regions from the variation in sequencing depth. RESULTS: Highly significant results (considering the number of genes in the genome) of the conventional burden test and the binomial performance deviation analysis overlapped significantly. Fourteen genes were highly significant by one method and confirmed with Bonferroni-corrected significance by the other to show a differential burden of low-frequency and rare variants in restless legs syndrome. Nine of them (AAGAB, ATP2C1, CNTN4, COL6A6, CRBN, GLO1, NTNG1, STEAP4, VAV3) resided in the vicinity of known restless legs syndrome loci, whereas 5 (BBS7, CADM1, CREB5, NRG3, SUN1) have not previously been associated with restless legs syndrome. Burden test and binomial performance deviation analysis also converged significantly in fine-mapping potentially causative domains within these genes. INTERPRETATION: Differential burden with intragenic low-frequency variants reveals putatively causative genes in restless legs syndrome. ANN NEUROL 2019."],["dc.identifier.doi","10.1002/ana.25658"],["dc.identifier.eissn","1531-8249"],["dc.identifier.isbn","31788832"],["dc.identifier.issn","0364-5134"],["dc.identifier.pmid","31788832"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17073"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/92063"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.relation.eissn","1531-8249"],["dc.relation.issn","1531-8249"],["dc.relation.issn","0364-5134"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.subject.ddc","610"],["dc.title","Identification of Restless Legs Syndrome Genes by Mutational Load Analysis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","898"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","The Lancet Neurology"],["dc.bibliographiccitation.lastpage","907"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Schormair, Barbara"],["dc.contributor.author","Zhao, Chen"],["dc.contributor.author","Bell, Steven"],["dc.contributor.author","Tilch, Erik"],["dc.contributor.author","Salminen, Aaro V"],["dc.contributor.author","Pütz, Benno"],["dc.contributor.author","Dauvilliers, Yves"],["dc.contributor.author","Stefani, Ambra"],["dc.contributor.author","Högl, Birgit"],["dc.contributor.author","Poewe, Werner"],["dc.contributor.author","Kemlink, David"],["dc.contributor.author","Sonka, Karel"],["dc.contributor.author","Bachmann, Cornelius G"],["dc.contributor.author","Paulus, Walter"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Oertel, Wolfgang H"],["dc.contributor.author","Hornyak, Magdolna"],["dc.contributor.author","Teder-Laving, Maris"],["dc.contributor.author","Metspalu, Andres"],["dc.contributor.author","Hadjigeorgiou, Georgios M"],["dc.contributor.author","Polo, Olli"],["dc.contributor.author","Fietze, Ingo"],["dc.contributor.author","Ross, Owen A"],["dc.contributor.author","Wszolek, Zbigniew"],["dc.contributor.author","Butterworth, Adam S"],["dc.contributor.author","Soranzo, Nicole"],["dc.contributor.author","Ouwehand, Willem H"],["dc.contributor.author","Roberts, David J"],["dc.contributor.author","Danesh, John"],["dc.contributor.author","Allen, Richard P"],["dc.contributor.author","Earley, Christopher J"],["dc.contributor.author","Ondo, William G"],["dc.contributor.author","Xiong, Lan"],["dc.contributor.author","Montplaisir, Jacques"],["dc.contributor.author","Gan-Or, Ziv"],["dc.contributor.author","Perola, Markus"],["dc.contributor.author","Vodicka, Pavel"],["dc.contributor.author","Dina, Christian"],["dc.contributor.author","Franke, Andre"],["dc.contributor.author","Tittmann, Lukas"],["dc.contributor.author","Stewart, Alexandre F R"],["dc.contributor.author","Shah, Svati H"],["dc.contributor.author","Gieger, Christian"],["dc.contributor.author","Peters, Annette"],["dc.contributor.author","Rouleau, Guy A"],["dc.contributor.author","Berger, Klaus"],["dc.contributor.author","Oexle, Konrad"],["dc.contributor.author","Di Angelantonio, Emanuele"],["dc.contributor.author","Hinds, David A"],["dc.contributor.author","Müller-Myhsok, Bertram"],["dc.contributor.author","Winkelmann, Juliane"],["dc.contributor.author","Balkau, B"],["dc.contributor.author","Ducimetière, P"],["dc.contributor.author","Eschwège, E"],["dc.contributor.author","Rancière, F"],["dc.contributor.author","Alhenc-Gelas, F"],["dc.contributor.author","Gallois, Y"],["dc.contributor.author","Girault, A"],["dc.contributor.author","Fumeron, F"],["dc.contributor.author","Marre, M"],["dc.contributor.author","Roussel, R"],["dc.contributor.author","Bonnet, F"],["dc.contributor.author","Bonnefond, A"],["dc.contributor.author","Cauchi, S"],["dc.contributor.author","Froguel, P"],["dc.contributor.author","Cogneau, J"],["dc.contributor.author","Born, C"],["dc.contributor.author","Caces, E"],["dc.contributor.author","Cailleau, M"],["dc.contributor.author","Lantieri, O"],["dc.contributor.author","Moreau, JG"],["dc.contributor.author","Rakotozafy, F"],["dc.contributor.author","Tichet, J"],["dc.contributor.author","Vol, S"],["dc.contributor.author","Agee, Michelle"],["dc.contributor.author","Alipanahi, Babak"],["dc.contributor.author","Auton, Adam"],["dc.contributor.author","Bell, Robert K"],["dc.contributor.author","Bryc, Katarzyna"],["dc.contributor.author","Elson, Sarah L"],["dc.contributor.author","Fontanillas, Pierre"],["dc.contributor.author","Furlotte, Nicholas A"],["dc.contributor.author","Hromatka, Bethann S"],["dc.contributor.author","Huber, Karen E"],["dc.contributor.author","Kleinman, Aaron"],["dc.contributor.author","Litterman, Nadia K"],["dc.contributor.author","McIntyre, Matthew H"],["dc.contributor.author","Mountain, Joanna L"],["dc.contributor.author","Northover, Carrie AM"],["dc.contributor.author","Pitts, Steven J"],["dc.contributor.author","Sathirapongsasuti, J Fah"],["dc.contributor.author","Sazonova, Olga V"],["dc.contributor.author","Shelton, Janie F"],["dc.contributor.author","Shringarpure, Suyash"],["dc.contributor.author","Tian, Chao"],["dc.contributor.author","Tung, Joyce Y"],["dc.contributor.author","Vacic, Vladimir"],["dc.contributor.author","Wilson, Catherine H"],["dc.date.accessioned","2020-12-10T15:22:02Z"],["dc.date.available","2020-12-10T15:22:02Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1016/S1474-4422(17)30327-7"],["dc.identifier.issn","1474-4422"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14927"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73253"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e79145"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Schulte, Eva C."],["dc.contributor.author","Stahl, Immanuel"],["dc.contributor.author","Czamara, Darina"],["dc.contributor.author","Ellwanger, Daniel C."],["dc.contributor.author","Eck, Sebastian H."],["dc.contributor.author","Graf, Elisabeth"],["dc.contributor.author","Mollenhauer, Brit"],["dc.contributor.author","Zimprich, Alexander"],["dc.contributor.author","Lichtner, Peter"],["dc.contributor.author","Haubenberger, Dietrich"],["dc.contributor.author","Pirker, Walter"],["dc.contributor.author","Bruecke, Thomas"],["dc.contributor.author","Bereznai, Benjamin"],["dc.contributor.author","Molnar, Maria J."],["dc.contributor.author","Peters, Annette"],["dc.contributor.author","Gieger, Christian"],["dc.contributor.author","Mueller-Myhsok, Bertram"],["dc.contributor.author","Trenkwalder, Claudia"],["dc.contributor.author","Winkelmann, Juliane"],["dc.date.accessioned","2018-11-07T09:17:37Z"],["dc.date.available","2018-11-07T09:17:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Approximately 20% of individuals with Parkinson's disease (PD) report a positive family history. Yet, a large portion of causal and disease-modifying variants is still unknown. We used exome sequencing in two affected individuals from a family with late-onset familial PD followed by frequency assessment in 975 PD cases and 1014 ethnically-matched controls and linkage analysis to identify potentially causal variants. Based on the predicted penetrance and the frequencies, a variant in PLXNA4 proved to be the best candidate and PLXNA4 was screened for additional variants in 862 PD cases and 940 controls, revealing an excess of rare non-synonymous coding variants in PLXNA4 in individuals with PD. Although we cannot conclude that the variant in PLXNA4 is indeed the causative variant, these findings are interesting in the light of a surfacing role of axonal guidance mechanisms in neurodegenerative disorders but, at the same time, highlight the difficulties encountered in the study of rare variants identified by next-generation sequencing in diseases with autosomal dominant or complex patterns of inheritance."],["dc.identifier.doi","10.1371/journal.pone.0079145"],["dc.identifier.isi","000327221600113"],["dc.identifier.pmid","24244438"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9507"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/28210"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Rare Variants in PLXNA4 and Parkinson's Disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]