Blood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome.
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-...
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2014
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oai:doaj.org-article:dcd845a0744e4f0b8a8dd1202187450a2021-11-18T08:17:52ZBlood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome.1932-620310.1371/journal.pone.0098092https://doaj.org/article/dcd845a0744e4f0b8a8dd1202187450a2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24875634/?tool=EBIhttps://doaj.org/toc/1932-6203Restless 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.Eva C SchulteKatharina SchrammClaudia SchurmannPeter LichtnerChristian HerderMichael RodenChristian GiegerAnnette PetersClaudia TrenkwalderBirgit HöglBirgit FrauscherKlaus BergerIngo FietzeNadine GrossKarin Stiasny-KolsterWolfgang OertelCornelius G BachmannWalter PaulusAlexander ZimprichHenry VölzkeUlf SchminkeMatthias NauckThomas IlligThomas MeitingerBertram Müller-MyhsokHolger ProkischJuliane WinkelmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 5, p e98092 (2014) |
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Medicine R Science Q Eva C Schulte Katharina Schramm Claudia Schurmann Peter Lichtner Christian Herder Michael Roden Christian Gieger Annette Peters Claudia Trenkwalder Birgit Högl Birgit Frauscher Klaus Berger Ingo Fietze Nadine Gross Karin Stiasny-Kolster Wolfgang Oertel Cornelius G Bachmann Walter Paulus Alexander Zimprich Henry Völzke Ulf Schminke Matthias Nauck Thomas Illig Thomas Meitinger Bertram Müller-Myhsok Holger Prokisch Juliane Winkelmann Blood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome. |
| description |
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. |
| format |
article |
| author |
Eva C Schulte Katharina Schramm Claudia Schurmann Peter Lichtner Christian Herder Michael Roden Christian Gieger Annette Peters Claudia Trenkwalder Birgit Högl Birgit Frauscher Klaus Berger Ingo Fietze Nadine Gross Karin Stiasny-Kolster Wolfgang Oertel Cornelius G Bachmann Walter Paulus Alexander Zimprich Henry Völzke Ulf Schminke Matthias Nauck Thomas Illig Thomas Meitinger Bertram Müller-Myhsok Holger Prokisch Juliane Winkelmann |
| author_facet |
Eva C Schulte Katharina Schramm Claudia Schurmann Peter Lichtner Christian Herder Michael Roden Christian Gieger Annette Peters Claudia Trenkwalder Birgit Högl Birgit Frauscher Klaus Berger Ingo Fietze Nadine Gross Karin Stiasny-Kolster Wolfgang Oertel Cornelius G Bachmann Walter Paulus Alexander Zimprich Henry Völzke Ulf Schminke Matthias Nauck Thomas Illig Thomas Meitinger Bertram Müller-Myhsok Holger Prokisch Juliane Winkelmann |
| author_sort |
Eva C Schulte |
| title |
Blood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome. |
| title_short |
Blood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome. |
| title_full |
Blood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome. |
| title_fullStr |
Blood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome. |
| title_full_unstemmed |
Blood cis-eQTL analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome. |
| title_sort |
blood cis-eqtl analysis fails to identify novel association signals among sub-threshold candidates from genome-wide association studies in restless legs syndrome. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2014 |
| url |
https://doaj.org/article/dcd845a0744e4f0b8a8dd1202187450a |
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