Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2014 May 29;9(5):e98092. doi: 10.1371/journal.pone.0098092. eCollection 2014.

Blood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome.

Author information

1
Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany.
2
Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany; Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
3
Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt Universität Greifswald, Greifswald, Germany.
4
Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
5
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), partner Düsseldorf, Düsseldorf, Germany.
6
Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), partner Düsseldorf, Düsseldorf, Germany; University Clinics of Endocrinology and Diabetology, University Hospital Düsseldorf, Düsseldorf, Germany.
7
Institute for Genetic Epidemiology, Helmholtz Zentrum München, Munich, Germany.
8
Institute for Epidemiology II, Helmholtz Zentrum München, Munich, Germany.
9
Paracelsus Elena Klinik, Kassel, Germany; Department of Neurosurgery, University Medical Center, Georg August Universität Göttingen, Göttingen, Germany.
10
Neurologische Klinik, Medizinische Universität Innsbruck, Innsbruck, Austria.
11
Institut für Epidemiologie und Sozialmedizin, Westfälische Wilhelms Universität Münster, Münster, Germany.
12
Zentrum für Schlafmedizin, Charite Universitätsmedizin, Berlin, Germany.
13
Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
14
Neurologische Klinik, Philips Universität Marburg, Marburg, Germany; Somnomar Institut für Medizinische Forschung und Schlafmedizin, Marburg, Germany.
15
Neurologische Klinik, Philips Universität Marburg, Marburg, Germany.
16
Abteilung für Neurologie, Paracelsus Klinik Osnabrück, Osnabrück, Germany.
17
Department of Clinical Neurophysiology, University Medical Center, Georg August Universität Göttingen, Göttingen, Germany.
18
Neurologische Klinik, Medizinische Universität Wien, Vienna, Austria.
19
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
20
Institute of Neurology, University Medicine Greifswald, Greifswald, Germany.
21
Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
22
Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Munich, Germany; Hannover Unified Biobank, Hannover Medical School, Hannover, Germany.
23
Max-Planck Institute for Psychiatry, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
24
Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany; Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

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 pnominal<10(-3) were identified, while in 976 individuals belonging to the SHIP-TREND general population study 53 cis-eQTLs with pnominal<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.

PMID:
24875634
PMCID:
PMC4038519
DOI:
10.1371/journal.pone.0098092
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center