Browse
Submit Data
Databases
API
Help

Dataset Information

42 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate.

ABSTRACT: Restless legs syndrome (RLS) is a common neurological condition with three loci (12q, 14q, and 9p) described so far, although none of these genes has yet been identified. We report a genomewide linkage scan of patients with RLS (n=37) assessed in a population isolate (n=530) of South Tyrol (Italy). Using both nonparametric and parametric analyses, we initially obtained suggestive evidence of a novel locus on chromosome 2q, with nominal evidence of linkage on chromosomes 5p and 17p. Follow-up genotyping yielded significant evidence of linkage (nonparametric LOD score 5.5, P

SUBMITTER: Pichler I

PROVIDER: S-EPMC1592574 | biostudies-literature | 2006 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Linkage analysis identifies a novel locus for restless legs syndrome on chromosome 2q in a South Tyrolean population isolate.

Pichler Irene I Marroni Fabio F Volpato Claudia Beu CB Gusella James F JF Klein Christine C Casari Giorgio G De Grandi Alessandro A Pramstaller Peter P PP

American journal of human genetics 20060814 4

Restless legs syndrome (RLS) is a common neurological condition with three loci (12q, 14q, and 9p) described so far, although none of these genes has yet been identified. We report a genomewide linkage scan of patients with RLS (n=37) assessed in a population isolate (n=530) of South Tyrol (Italy). Using both nonparametric and parametric analyses, we initially obtained suggestive evidence of a novel locus on chromosome 2q, with nominal evidence of linkage on chromosomes 5p and 17p. Follow-up gen ...[more]

PMID: 16960808

Similar Datasets

Genomewide linkage scan identifies a novel susceptibility locus for restless legs syndrome on chromosome 9p.

Project description:Restless legs syndrome (RLS) is a common neurological disorder that affects 5%-12% of all whites. To genetically dissect this complex disease, we characterized 15 large and extended multiplex pedigrees, consisting of 453 subjects (134 affected with RLS). A familial aggregation analysis was performed, and SAGE FCOR was used to quantify the total genetic contribution in these families. A weighted average correlation of 0.17 between first-degree relatives was obtained, and heritability was estimated to be 0.60 for all types of relative pairs, indicating that RLS is a highly heritable trait in this ascertained cohort. A genomewide linkage scan, which involved >400 10-cM-spaced markers and spanned the entire human genome, was then performed for 144 individuals in the cohort. Model-free linkage analysis identified one novel significant RLS-susceptibility locus on chromosome 9p24-22 with a multipoint nonparametric linkage (NPL) score of 3.22. Suggestive evidence of linkage was found on chromosome 3q26.31 (NPL score 2.03), chromosome 4q31.21 (NPL score 2.28), chromosome 5p13.3 (NPL score 2.68), and chromosome 6p22.3 (NPL score 2.06). Model-based linkage analysis, with the assumption of an autosomal-dominant mode of inheritance, validated the 9p24-22 linkage to RLS in two families (two-point LOD score of 3.77; multipoint LOD score of 3.91). Further fine mapping confirmed the linkage result and defined this novel RLS disease locus to a critical interval. This study establishes RLS as a highly heritable trait, identifies a novel genetic locus for RLS, and will facilitate further cloning and identification of the genes for RLS.

| S-EPMC1181982 | biostudies-literature

Suggestive evidence for linkage for restless legs syndrome on chromosome 19p13.

Project description:Five loci for restless legs syndrome (RLS) on chromosomes 12q, 14q, 9p, 2q, and 20p (RLS1-RLS5) have been mapped in RLS families, with a recessive in the first and autosomal-dominant mode of inheritance in the latter cases. Investigations of further RLS families showed evidence for genetic locus heterogeneity. We have conducted a genome-wide linkage analysis in a large RLS family of Italian origin with 12 affected members in 3 generations using 5,861 single nucleotide polymorphisms (SNP, 6K Illumina). Linkage analysis was performed under an autosomal-dominant model with a complete penetrance, an allele frequency of 0.003 and a phenocopy rate of 0.005. The genome-wide scan resulted in suggestive evidence for linkage on chromosome 19p with maximum multipoint logarithm of the odds score of 2.61 between markers rs754292 and rs273265. The locus was replicated in a family-based association study in a set of 159 trios of European origin. This study provides evidence for a further RLS locus, thus supporting the picture of RLS as a genetically heterogenous complex trait.

| S-EPMC2757615 | biostudies-literature

No convincing evidence of linkage for restless legs syndrome on chromosome 9p.

Project description: Not available

| S-EPMC1199308 | biostudies-literature

Restless legs syndrome.

Project description: Not available

| S-EPMC1557937 | biostudies-literature

Association of restless legs syndrome variants in Korean patients with restless legs syndrome.

Project description:STUDY OBJECTIVES: Recent genome-wide association studies (GWAS) for Caucasians identified several allelic variants associated with increased risk of developing restless legs syndrome (RLS), also known as Willis-Ekbom disease. Although the pathogenic mechanisms of RLS are not entirely understood, it is becoming increasingly evident that many diseases such as RLS can be attributed to an epistasis. The study objectives were to evaluate whether the associations of RLS with all loci determined in previous GWAS for Caucasians can be replicated significantly for the Korean population and to elucidate whether an epistasis plays a role in the pathogenesis of RLS. DESIGN SETTING AND PARTICIPANTS: DNA from 320 patients with RLS and 320 age- and sex-matched controls were genotyped for variants in the RLS loci. MEASUREMENTS AND RESULTS: A significant association was found for rs3923809 and rs9296249 in BTBD9 (P < 0.0001 and P = 0.001, respectively); the odds ratio (OR) for rs3923809 was 1.61 (P < 0.0001) to 1.88 (P < 0.0001) and the OR for rs9296249 was 1.44 (P = 0.001) to 1.73 (P = 0.002), according to the model of inheritance. The OR for the interaction between rs3923809 in BTBD9 and rs4626664 in PTPRD was 2.05 (P < 0.0001) in the additive model, 1.80 (P = 0.002) in the dominant model and 2.47 (P = 0.004) in the recessive model. There was no significant association between genotypes of all tested single nucleotide polymorphisms and the mean value of serum iron parameters. CONCLUSIONS: Our results suggest that the role of BTBD9 in the pathogenesis of restless legs syndrome is more universal across populations than previously reported and more efforts should be focused on the role of epistasis in the genetic architecture of restless legs syndrome.

| S-EPMC3825427 | biostudies-literature

Treatment of restless legs syndrome.

Project description:Restless legs syndrome (RLS) is a common disorder diagnosed by the clinical characteristics of restlessness in the legs associated often with abnormal sensations that start at rest and are improved by activity, occurring with a diurnal pattern of worsened symptoms at night and improvement in the morning. RLS is the cause of impaired quality of life in those more severely afflicted. Treatment of RLS has undergone considerable change over the last few years. Several classes of medications have demonstrated efficacy, including the dopaminergic agents and the alpha-2-delta ligands. Levodopa was the first dopaminergic agent found to be successful. However, chronic use of levodopa is frequently associated with augmentation that is defined as an earlier occurrence of symptoms frequently associated with worsening severity and sometimes spread to other body areas. The direct dopamine agonists, including ropinirole, pramipexole, and rotigotine patch, are also effective, although side effects, including daytime sleepiness, impulse control disorders, and augmentation, may limit usefulness. The alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur. Other agents, including the opioids and clonazepam do not have sufficient evidence to recommend them as treatment for RLS, although in an individual patient, they may provide benefit.

| S-EPMC3899490 | biostudies-literature

Iron in Restless Legs Syndrome.

Project description:A link between restless legs syndrome (RLS) and iron has been recognized for several decades. Yet, the precise role that iron or other components of iron metabolism play in bringing about RLS is still a matter of debate. During the last few years, many new pieces of evidence from genetics, pathology, imaging, and clinical studies have surfaced. However, the way this evidence fits into the larger picture of RLS as a disease is not always easily understood. To provide a better understanding of the complex interplay between iron metabolism and RLS and highlight areas that need further elucidation, we systematically and critically review the current literature on the role of iron in RLS pathophysiology and treatment with a special emphasis on genetics, neuropathology, cell and animal models, imaging studies, and therapy.

| S-EPMC6183309 | biostudies-literature

Large genome-wide association study identifies three novel risk variants for restless legs syndrome.

Project description:Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10-18), rs10068599-T (OR = 1.09, P = 6.9 × 10-10) and rs10769894-A (OR = 0.90, P = 9.4 × 10-14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed.

| S-EPMC7689502 | biostudies-literature

Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1.

Project description: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 × 10(-11), OR?=?1.23) and a locus on 16q12.1 (rs3104767, P?=?9.4 × 10(-19), OR?=?1.35) in a linkage disequilibrium block of 140 kb containing the 5'-end of TOX3 and the adjacent non-coding RNA BC034767.

| S-EPMC3136436 | biostudies-literature

Mesomelic dysplasia Kantaputra type is associated with duplications of the HOXD locus on chromosome 2q.

Project description:Mesomelic dysplasia Kantaputra type (MDK) is characterized by marked mesomelic shortening of the upper and lower limbs originally described in a Thai family. To identify the cause of MDK, we performed array CGH and identified two microduplications on chromosome 2 (2q31.1-q31.2) encompassing ?481 and 507 kb, separated by a segment of normal copy number. The more centromeric duplication encompasses the entire HOXD cluster, as well as the neighboring genes EVX2 and MTX2. The breakpoints of the duplication localize to the same region as the previously identified inversion of the mouse mutant ulnaless (Ul), which has a similar phenotype as MDK. We propose that MDK is caused by duplications that modify the topography of the locus and as such result in deregulation of HOXD gene expression.

| S-EPMC3002849 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data