scholarly journals Blood cis-eQTL Analysis Fails to Identify Novel Association Signals among Sub-Threshold Candidates from Genome-Wide Association Studies in Restless Legs Syndrome

PLoS ONE ◽  
2014 ◽  
Vol 9 (5) ◽  
pp. e98092 ◽  
Author(s):  
Eva C. Schulte ◽  
Katharina Schramm ◽  
Claudia Schurmann ◽  
Peter Lichtner ◽  
Christian Herder ◽  
...  
Keyword(s):  
Restless Legs Syndrome ◽  
Association Studies ◽  
Genome Wide Association ◽  
Eqtl Analysis ◽  
Genome Wide Association Studies ◽  
Restless Legs ◽  
Genome Wide ◽  
Novel Association

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

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Maria Didriksen ◽  
Muhammad Sulaman Nawaz ◽  
Joseph Dowsett ◽  
Steven Bell ◽  
Christian Erikstrup ◽  
...  
Keyword(s):  
Restless Legs Syndrome ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Polygenic Risk Score ◽  
Eqtl Analysis ◽  
Genome Wide Association Studies ◽  
Restless Legs ◽  
Genome Wide

AbstractRestless 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.

Latest Perspectives in Genetic Risk Factors for Restless Legs Syndrome

2013 ◽  
Vol 8 (2) ◽  
pp. 90 ◽  
Author(s):  
Félix Javier Jiménez-Jiménez ◽  
Hortensia Alonso-Navarro ◽  
Elena García-Martín ◽  
José AG Agûndez ◽  
◽  
...  
Keyword(s):  
Restless Legs Syndrome ◽  
Association Studies ◽  
Positive Family History ◽  
Twin Studies ◽  
Genome Wide Association Studies ◽  
Restless Legs ◽  
Genome Wide ◽  
History Of ◽  
High Concordance ◽  
Control Association

The high frequency of positive family history of restless legs syndrome (RLS) in patients with this disease and the observed high concordance rates in monozygotic compared with dizygotic twins support a major role of genetic factors in the development of RLS. Although a number of variants for several genes may increase the risk of RLS, no definitive causative genes have been identified to date. In this review, we summarise the studies performed on families with RLS, twin studies, linkage studies, genome-wide association studies, case-control association studies and exome sequencing in RLS. The strongest candidate genes are ofPTPRD, BTBD9andMEIS.

scholarly journals Genome-Wide Association between the 2q33.1 Locus and Intracranial Aneurysm Susceptibility: An Updated Meta-Analysis Including 18,019 Individuals

2019 ◽  
Vol 8 (5) ◽  
pp. 692
Author(s):  
Eun Pyo Hong ◽  
Bong Jun Kim ◽  
Jin Pyeong Jeon
Keyword(s):  
Intracranial Aneurysm ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Eqtl Analysis ◽  
Genome Wide Association Studies ◽  
Human Tissues ◽  
Genome Wide ◽  
A Genome

Previous genome-wide association studies did not show a consistent association between the BOLL gene (rs700651, 2q33.1) and intracranial aneurysm (IA) susceptibility. We aimed to perform an updated meta-analysis for the potential IA-susceptibility locus in large-scale multi-ethnic populations. We conducted a systematic review of studies identified by an electronic search from January 1990 to March 2019. The overall estimates of the “G” allele of rs700651, indicating IA susceptibility, were calculated under the fixed- and random-effect models using the inverse-variance method. Subsequent in silico function and cis-expression quantitative trait loci (cis-eQTL) analyses were performed to evaluate biological functions and genotype-specific expressions in human tissues. We included 4513 IA patients and 13,506 controls from five studies with seven independent populations: three European-ancestry, three Japanese, and one Korean population. The overall result showed a genome-wide significance threshold between rs700651 and IA susceptibility after controlling for study heterogeneity (OR = 1.213, 95% CI: 1.135–1.296). Subsequent cis-eQTL analysis showed significant genome-wide expressions in three human tissues, i.e., testis (p = 8.04 × 10−15 for ANKRD44), tibial nerves (p = 3.18 × 10−10 for SF3B1), and thyroid glands (p = 4.61 × 10−9 for SF3B1). The rs700651 common variant of the 2q33.1 region may be involved in genetic mechanisms that increase the risk of IA and may play crucial roles in regulatory functions.

scholarly journals Pharmacologic treatment of restless legs syndrome

2020 ◽  
Vol 19 ◽  
Author(s):  
Qing Lv ◽  
Xinlin Wang ◽  
Tetsuya Asakawa ◽  
Xiao Ping Wang
Keyword(s):  
Restless Legs Syndrome ◽  
Association Studies ◽  
Cell Loss ◽  
Genome Wide Association Studies ◽  
Neural Pathways ◽  
Dopaminergic Drugs ◽  
Restless Legs ◽  
Genome Wide ◽  
Mechanistic Basis

: Restless legs syndrome (RLS)/Willis-Ekbom disease is a neurologic disorder characterized by a strong desire to move when at rest (usually in the evening) and paraesthesia in their lower legs. The most widely used therapies for first-line treatment of RLS are dopaminergic drugs; however, their long-term use can lead to augmentation. α2δ Ligands, opioids, iron, glutamatergic drugs, adenosine, and sleep aids have been investigated as alternatives. The pathogenesis of RLS is not well understood. Despite the efficacy of dopaminergic drugs in the treatment of this disorder, unlike in Parkinson’s disease dopaminergic cell loss in the substantia nigra has not been observed in RLS. The etiology of RLS is likely complex, involving multiple neural pathways. RLS-related genes identified in genome-wide association studies can provide insight into the mechanistic basis and pathophysiology of RLS. Here we review the current treatments and knowledge of the mechanisms underlying RLS.

scholarly journals Unraveling the polygenic architecture of complex traits using blood eQTL metaanalysis

2018 ◽  
Author(s):  
Urmo Võsa ◽  
Annique Claringbould ◽  
Harm-Jan Westra ◽  
Marc Jan Bonder ◽  
Patrick Deelen ◽  
...  
Keyword(s):  
Complex Traits ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Complex Trait ◽  
Genome Wide Association ◽  
Eqtl Analysis ◽  
Genome Wide Association Studies ◽  
Disease Etiology ◽  
Genome Wide ◽  
Polygenic Scores

SummaryWhile many disease-associated variants have been identified through genome-wide association studies, their downstream molecular consequences remain unclear.To identify these effects, we performedcis-andtrans-expressionquantitative trait locus (eQTL) analysis in blood from 31,684 individuals through the eQTLGen Consortium.We observed thatcis-eQTLs can be detected for 88% of the studied genes, but that they have a different genetic architecture compared to disease-associated variants, limiting our ability to usecis-eQTLs to pinpoint causal genes within susceptibility loci.In contrast, trans-eQTLs (detected for 37% of 10,317 studied trait-associated variants) were more informative. Multiple unlinked variants, associated to the same complex trait, often converged on trans-genes that are known to play central roles in disease etiology.We observed the same when ascertaining the effect of polygenic scores calculated for 1,263 genome-wide association study (GWAS) traits. Expression levels of 13% of the studied genes correlated with polygenic scores, and many resulting genes are known to drive these traits.

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