Schulte Eva C, Schramm Katharina, Schurmann Claudia, Lichtner Peter, Herder Christian, Roden Michael, Gieger Christian, Peters Annette, Trenkwalder Claudia, Högl Birgit, Frauscher Birgit, Berger Klaus, Fietze Ingo, Gross Nadine, Stiasny-Kolster Karin, Oertel Wolfgang, Bachmann Cornelius G, Paulus Walter, Zimprich Alexander, Völzke Henry, Schminke Ulf, Nauck Matthias, Illig Thomas, Meitinger Thomas, Müller-Myhsok Bertram, Prokisch Holger, Winkelmann Juliane
Neurologische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany.
Institut für Humangenetik, Helmholtz Zentrum München, Munich, Germany; Institut für Humangenetik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
PLoS One. 2014 May 29;9(5):e98092. doi: 10.1371/journal.pone.0098092. eCollection 2014.
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.
不宁腿综合征（RLS）是一种常见的神经系统疾病，其特征为夜间感觉异常，主要在休息期间影响腿部，并通过活动缓解。RLS是一种复杂的遗传疾病，通过全基因组关联研究（GWAS）已在六个基因组区域鉴定出易感因素。对于一些复杂的遗传性状，表达数量性状位点（eQTL）在性状相关的单核苷酸多态性（SNP）中富集。为了确定RLS的新遗传易感因素，我们评估了来自迄今为止最大的RLS GWAS全基因组阶段的332个最佳关联SNP，以研究其在欧洲血统个体外周血中的顺式eQTL效应。在属于KORA普通人群队列的740名个体中，鉴定出52个名义p值<10⁻³的顺式eQTL，而在属于SHIP-TREND普通人群研究的976名个体中，存在53个名义p值<10⁻³的顺式eQTL。其中23个顺式eQTL在两个队列之间重叠。随后，对23个顺式eQTL SNP中未位于已发表的RLS相关位点的12个进行了2449例RLS病例和1462例对照的关联测试。位于DET1基因中的顶级SNP名义上具有显著性（p<0.05），但未通过多重检验校正（p = 0.42）。尽管类似的方法已成功应用于其他复杂疾病，但我们无法通过在RLS GWAS数据中增加这种新的功能评估水平来确定RLS的新遗传易感因素。
