Sequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation.
Sequence variant at 8q24.21 associates with sciatica caused by lumbar disc herniation.
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DOI：
10.1038/ncomms14265
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发表时间：
2017-02-22
影响因子：
16.6
通讯作者：
Stefansson K
中科院分区：
文献类型：
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作者：
Bjornsdottir G;Benonisdottir S;Sveinbjornsson G;Styrkarsdottir U;Thorleifsson G;Walters GB;Bjornsson A;Olafsson IH;Ulfarsson E;Vikingsson A;Hansdottir R;Karlsson KO;Rafnar T;Jonsdottir I;Frigge ML;Kong A;Oddsson A;Masson G;Magnusson OT;Gudbjartsson T;Stefansson H;Sulem P;Gudbjartsson D;Thorsteinsdottir U;Thorgeirsson TE;Stefansson K
腰椎间盘突出症(LDH)很常见，通常会使人虚弱。腰椎间盘突出症微创摘除术(LDHsurg)是在最严重的情况下进行的，以解决由此引起的坐骨神经痛。在这里，我们对4,748例LDHsurg病例和282,590例人群对照进行了全基因组关联研究，发现了37个与LDHsurg高度相关的标记，位于8q24.21(位于CCDC26和GSDMC之间)，以rs6651255[C]为代表(OR=0.81；P=5.6×10−12)，在年轻患者中的作用强于老年患者。由于rs6651255[C]也与身高相关，我们进行了孟德尔随机分析，使用身高多基因风险评分作为工具来估计身高对LDHsurg风险的影响，发现该标记与LDHsurg的关联远远大于其对身高的影响所预测的。根据目前的研究结果，我们推测rs6651255对LDH的影响是由LDH对严重和持续性坐骨神经痛的易感性驱动的。腰椎间盘突出症(LDH)会导致持续性坐骨神经痛，在某些情况下需要手术来缓解症状。在这里，作者进行了一项全基因组关联研究，使用微椎间盘切除作为严重LDH的指标，并在8号染色体上找到了与这种情况相关的基因。
Lumbar disc herniation (LDH) is common and often debilitating. Microdiscectomy of herniated lumbar discs (LDHsurg) is performed on the most severe cases to resolve the resulting sciatica. Here we perform a genome-wide association study on 4,748 LDHsurg cases and 282,590 population controls and discover 37 highly correlated markers associating with LDHsurg at 8q24.21 (between CCDC26 and GSDMC), represented by rs6651255[C] (OR=0.81; P=5.6 × 10−12) with a stronger effect among younger patients than older. As rs6651255[C] also associates with height, we performed a Mendelian randomization analysis using height polygenic risk scores as instruments to estimate the effect of height on LDHsurg risk, and found that the marker's association with LDHsurg is much greater than predicted by its effect on height. In light of presented findings, we speculate that the effect of rs6651255 on LDHsurg is driven by susceptibility to developing severe and persistent sciatica upon LDH. Lumbar disc herniation (LDH) can cause persistent sciatica, and in some cases surgery is required to relieve symptoms. Here, the authors carry out a genome-wide association study using microdiscectomy as an indicator of severe LDH, and find a locus on chromosome 8 associated with this condition.