全基因组关联分析鉴定出脑膜瘤风险位点位于 11p15.5。
Genome-wide association analysis identifies a meningioma risk locus at 11p15.5.
机构信息
School of Public Health, Yale University, New Haven, Connecticut, USA.
Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
出版信息
Neuro Oncol. 2018 Oct 9;20(11):1485-1493. doi: 10.1093/neuonc/noy077.
BACKGROUND
Meningiomas are adult brain tumors originating in the meningeal coverings of the brain and spinal cord, with significant heritable basis. Genome-wide association studies (GWAS) have previously identified only a single risk locus for meningioma, at 10p12.31.
METHODS
To identify a susceptibility locus for meningioma, we conducted a meta-analysis of 2 GWAS, imputed using a merged reference panel from the 1000 Genomes Project and UK10K data, with validation in 2 independent sample series totaling 2138 cases and 12081 controls.
RESULTS
We identified a new susceptibility locus for meningioma at 11p15.5 (rs2686876, odds ratio = 1.44, P = 9.86 × 10-9). A number of genes localize to the region of linkage disequilibrium encompassing rs2686876, including RIC8A, which plays a central role in the development of neural crest-derived structures, such as the meninges.
CONCLUSIONS
This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.
背景
脑膜瘤是起源于脑和脊髓脑膜覆盖物的成人脑肿瘤，具有显著的遗传基础。全基因组关联研究（GWAS）先前仅确定了脑膜瘤的一个单一风险位点，位于 10p12.31。
方法
为了确定脑膜瘤的易感性位点，我们对 2 项 GWAS 进行了荟萃分析，使用来自 1000 基因组计划和 UK10K 数据的合并参考面板进行了推断，并在 2 个独立的样本系列中进行了验证，总共有 2138 例病例和 12081 例对照。
结果
我们在 11p15.5 上确定了一个新的脑膜瘤易感性位点（rs2686876，优势比=1.44，P=9.86×10-9）。一些基因定位于包含 rs2686876 的连锁不平衡区域，包括 RIC8A，它在神经嵴衍生结构（如脑膜）的发育中起着核心作用。
结论
这一发现提高了我们对脑膜瘤发生的遗传基础的理解，并为脑膜瘤的多基因模型提供了额外的支持。
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