School of Public Health, Yale University, New Haven, Connecticut, USA.
Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Neuro Oncol. 2018 Oct 9;20(11):1485-1493. doi: 10.1093/neuonc/noy077.
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.
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.
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.
This finding advances our understanding of the genetic basis of meningioma development and provides additional support for a polygenic model of meningioma.
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。
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。
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。
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。
