Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1.
Genome-wide association study identifies novel restless legs syndrome susceptibility loci on 2p14 and 16q12.1.
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DOI：
10.1371/journal.pgen.1002171
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发表时间：
2011-07
期刊：
影响因子：
4.5
通讯作者：
Meitinger T
中科院分区：
文献类型：
--
作者：
Winkelmann J;Czamara D;Schormair B;Knauf F;Schulte EC;Trenkwalder C;Dauvilliers Y;Polo O;Högl B;Berger K;Fuhs A;Gross N;Stiasny-Kolster K;Oertel W;Bachmann CG;Paulus W;Xiong L;Montplaisir J;Rouleau GA;Fietze I;Vávrová J;Kemlink D;Sonka K;Nevsimalova S;Lin SC;Wszolek Z;Vilariño-Güell C;Farrer MJ;Gschliesser V;Frauscher B;Falkenstetter T;Poewe W;Allen RP;Earley CJ;Ondo WG;Le WD;Spieler D;Kaffe M;Zimprich A;Kettunen J;Perola M;Silander K;Cournu-Rebeix I;Francavilla M;Fontenille C;Fontaine B;Vodicka P;Prokisch H;Lichtner P;Peppard P;Faraco J;Mignot E;Gieger C;Illig T;Wichmann HE;Müller-Myhsok B;Meitinger T
不宁腿综合征（RLS）是一种感觉运动障碍，在65岁以上的普通人群中，其年龄依赖性患病率高达10%。受影响的个体遭受不舒服的感觉和下肢运动的冲动，主要发生在晚上或夜间的休息情况下。移动腿或走路可以改善症状。同时，患者报告睡眠障碍的后果，如减少日间功能。我们在922例病例和1,526例对照中进行了RLS的全基因组关联研究（GWA）（使用301,406个SNP），随后在3,935例病例和5,754例对照中复制了76个候选SNP，所有病例和对照都是欧洲血统。在此，我们确定了6个具有全基因组意义的RLS易感基因座，其中两个是新的：染色体2 p14上的基因间区域（rs6747972，P = 9.03 × 10−11，OR = 1.23）和16q12.1上的基因座（rs3104767，P = 9.4 × 10−19，OR = 1.35），位于140 kb的连锁不平衡区，包含TOX 3的5′端和相邻的非编码RNA BC 034767。 不宁腿综合征（RLS）是最常见的神经系统疾病之一。RLS患者有移动腿部的冲动，并且大多数情况下小腿深处有不愉快的感觉。症状主要发生在晚上或夜间休息的情况下。因此，睡眠的启动和维持变得有缺陷。在这里，我们进行了一项全基因组关联研究，以确定增加疾病风险的常见遗传变异。全基因组阶段包括922例病例和1，526例对照，候选SNP在3，935例病例和5，754例对照中重复，所有病例均为欧洲血统。我们发现了两个新的RLS相关基因座：染色体2 p14上的基因间区域和16q12.1上的一个基因座，该基因座位于包含TOX 3的5′端和相邻的非编码RNA BC 034767的连锁不平衡块中。TOX 3与乳腺癌的发展有关。TOX 3和BC 034767在中枢神经系统中的生理作用以及这两个基因在RLS发病机制中的可能参与仍有待确定。
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. Restless legs syndrome (RLS) is one of the most common neurological disorders. Patients with RLS suffer from an urge to move the legs and unpleasant sensations located mostly deep in the calf. Symptoms mainly occur in resting situations in the evening or at night. As a consequence, initiation and maintenance of sleep become defective. Here, we performed a genome-wide association study to identify common genetic variants increasing the risk for disease. The genome-wide phase included 922 cases and 1,526 controls, and candidate SNPs were replicated in 3,935 cases and 5,754 controls, all of European ancestry. We identified two new RLS–associated loci: an intergenic region on chromosome 2p14 and a locus on 16q12.1 in a linkage disequilibrium block containing the 5′-end of TOX3 and the adjacent non-coding RNA BC034767. TOX3 has been implicated in the development of breast cancer. The physiologic role of TOX3 and BC034767 in the central nervous system and a possible involvement of these two genes in RLS pathogenesis remain to be established.
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DOI：
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发表时间：
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影响因子：
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